An examination of nerve-mediated, hyoscine-resistant excitation of the guinea-pig colon. 1. The mechanical and electrical activity of the smooth muscle of the distal colon of the guinea-pig has been recorded in experiments designed to determine the nature of the nerve-mediated excitation of the muscle.2. The spontaneous contractions of the colon, normally observed in vitro, were similarly antagonized by hyoscine or tetrodotoxin. However, neither drug caused complete cessation of the spontaneous activity.3. The contractile responses of the colon to repetitive stimulation of intramural nerve fibres were of two types, a primary contraction which occurred within 1 sec of the beginning of stimulation and a secondary contraction which occurred after stimulation. The primary contraction was blocked by hyoscine, usually revealing an inhibitory response to stimulation, but the secondary contraction persisted. Similar primary contractions were observed in response to stimulation of the pelvic and sometimes of the periarterial nerves.4. An initial relaxation during, and a secondary contraction after, stimulation were sometimes obtained when the periarterial nerves were stimulated. Propranolol completely blocked both the initial relaxation and the secondary contraction in response to sympathetic stimulation but did not affect either the relaxation or the secondary contraction in response to transmural stimulation.5. The direct effects of noradrenaline and adenosine triphosphate on the mechanical activity of the colon were studied. Both drugs caused a relaxation of the colon. Washout of either drug after a short exposure was followed by a period of increased activity. Especially in preparations of low tone, the initial relaxation and the secondary contraction in response to transmural stimulation could be mimicked by the application and washout of either noradrenaline or adenosine triphosphate.6. Two types of potential change were evoked in the muscle cells of the colon, either separately or in combination, when the intramural nerve fibres were stimulated: excitatory junction potentials (EJPs), which were blocked by hyoscine, and inhibitory junction potentials (IJPs). When the membrane potential recovered following an IJP, it was common to observe action potentials in muscle cells that were initially quiescent. A similar secondary firing of action potentials was initiated by hyperpolarizing the muscle cells with anodal current pulses in the presence of tetrodotoxin in sufficient concentration to block nerve-mediated responses.7. The results reported in this paper lead to the conclusion that the muscle cells of the distal colon of the guinea-pig are influenced by three sets of nerves: cholinergic excitatory, adrenergic inhibitory and intrinsic inhibitory fibres releasing a non-adrenergic transmitter substance. The secondary non-cholinergic excitation arises from a non-specific reaction of the muscle cells to a preceding inhibition.


Spontaneous and evoked single unit activity in 7-day rat cerebral cortex.


Simultaneous measurement of cardiac output and mean arterial pressure changes in unanaesthetized rats.


Further study of the role of calcium in synaptic transmission. 1. The effect of calcium on synaptic transmission has been studied by intracellular recording of pre- and post-synaptic potential changes in the stellate ganglion of the squid.2. For a given presynaptic ;input' (propagated spike, or local depolarizing pulse after tetrodotoxin treatment), the post-synaptic response increases with external calcium concentration [Ca](o) in a highly non-linear fashion, indicating that transmitter output varies with more than the second power of [Ca](o) over a certain concentration range.


The frequency of nerve impulses in single carotid body chemoreceptor afferent fibres recorded in vivo with intact circulation. 1. The responses of single afferent fibres of carotid body chemoreceptors to independent changes in arterial O(2) and CO(2) tensions and pH were studied in the cat in vivo.2. The response curve obtained relating chemoreceptor activity to changes in arterial P(O2) was similar to an hyperbola; the frequency of nerve impulses at first decreased rapidly as the P(a,O2) was raised and then more slowly. The arterial P(O2) at which the slow decrease was reached varied among the different fibres; the mean level was 190 mm Hg (S.D. +/- 40 mm Hg).3. Single chemoreceptor afferent fibres continued to discharge even when the arterial P(O2) was more than 600 mm Hg.4. The discharges of single chemoreceptor afferent fibres increased both with increasing P(a,CO2) at constant pH and P(a,O2), and with increasing arterial H(+) at constant P(a,CO2) and P(a,O2).5. It is concluded that single carotid body chemoreceptor afferent fibres of the cat can be activated in vivo by an increase in either arterial H(+) or arterial P(CO2) as well as by a decrease in arterial P(O2).


Vocal behaviour of new-born rats as a means of recording time of birth.


Electron microscopic and electrophysiological studies on the carotid body following intracranial section of the glossopharyngeal nerve. 1. The innervation of carotid body Type I cells has been investigated in seventeen cats. At a sterile operation the glossopharyngeal and vagus nerve roots were cut intracranially on one side.2. From 1(1/2) to 378 days after the operation the carotid bodies were fixed in situ and prepared for electron microscopy. Nerve endings on Type I cells were found to degenerate with a prolonged time course. In each cat there was a decrease in the number of nerve endings on the operated side as compared with the non-operated side.3. Before the carotid bodies were fixed, recordings were made from chemoreceptor, and baroreceptor, afferent fibres in the sinus nerve on the operated side. The chemoreceptors responded in the usual way to changes in arterial O(2), CO(2) and pH; the injection of cyanide evoked a brisk response.4. It is concluded that the nerve endings on Type I cells are efferent rather than afferent and the cell bodies of their axons are probably in the brain stem.


A possible diurnal rhythm in rat pancreatic secretion.


Haematological effects of moderate blood loss in healthy medical students.


The ontogenesis of haematoencephalic cation transport processes in the rhesus monkey. 1. This investigation was undertaken to determine the time course of development of cation transport processes between blood and the extracellular fluid compartments of the central nervous system (C.N.S.) of the foetal rhesus monkey. The development of concentration gradients within the cerebrospinal fluid (c.s.f.) system was also studied in an attempt to gain information on regional variations in transport activities.2. Cerebrospinal fluid samples were obtained from the lateral ventricle, the cisterna magna, the cortical subarachnoid space and the lumbar region of the spinal subarachnoid space of adult monkeys. Foetal c.s.f. samples were obtained from the cisterna magna and the frontal region of the cortical subarachnoid space. Blood samples were taken within 3-10 min of the c.s.f. samples. The concentration of K, Mg and Ca were determined on appropriately diluted samples by atomic absorption spectrophotometry.3. The concentrations of K, Mg, and Ca in the plasma and c.s.f.s of the adult monkey are similar to those of other mammalian species. The c.s.f./blood concentration gradients of these cations are in the same direction but generally of greater magnitude than those in non-primate mammals. The indicated [Mg] in the extracellular fluid of the adult monkey's cerebral cortex is high (more than 2 m-equiv/kg H(2)O) and the [K] is low (less than 2 m-equiv/kg H(2)O).4. Accumulation of Mg into the c.s.f. system against a concentration gradient is evident in the earliest foetuses studied (50 days of intrauterine life) and by the second half of gestation the concentration gradients of this cation are similar to that of the adult.5. In the second trimester foetus, the [K] in the cisternal fluid is near the plasma ultrafiltrate level. It then decreases gradually throughout the remainder of gestation, approximating the adult value at birth.6. The very low [K] typical of the adult cortical subarachnoid fluid is observed by the sixth month following birth but not during foetal life or within the first few weeks of post-natal life. This indicates that the transport processes at the cortical region of the haematoencephalic interphase do not fully develop until well after birth.7. It is concluded that the various transport processes responsible for the elaboration and maintenance of adult type of K, Ca and Mg concentrations within the extracellular fluid compartments of the monkey C.N.S. do not develop at the same time. This temporal dissociation provides strong evidence against any direct association or coupling between the haematoencephalic K and Mg transport systems.8. Existence of normal cation concentration gradients between c.s.f. and blood may serve as a criterion for the normality of the (foetal) blood-brain barrier.


Active potassium transport in the immature red cells of anaemic sheep.


Ouabain-sensitive carrier-mediated transport of glucose from the cerebral ventricles to surrounding tissues in the cat. 1. Artificial cerebrospinal fluid containing isotopically labelled sugars was perfused from the lateral cerebral ventricles to an effluent catheter inserted into the cerebral aqueduct of anaesthetized cats. This system was used for a quantitative study of the absorption of the sugars during steady state.2. A saturable mechanism was involved in the absorption of [U-(14)C]D-glucose and [(14)C]D-galactose. Absorption of [U-(14)C]D-glucose in the dead animal was similar to that of [(3)H]D-mannitol.3. 5 x 10(-5)M ouabain in the inflow reduced cerebrospinal fluid formation and the unidirectional fluxes of glucose from the ventricles into brain tissue and plasma. Ouabain did not alter the absorption of [(3)H]D-mannitol.4. Three types of unidirectional fluxes of glucose from the cerebral ventricles were separated. One was ouabain-sensitive and followed Michaelis-Menten kinetics. The second was insensitive to ouabain and the third occurred by simple diffusion.5. At normal ventricular glucose concentrations (3.5 mM) the three fluxes comprised (roughly): 25% (ouabain-sensitive), 35% (ouabain-insensitive) and 40% (simple diffusion) of total, unidirectional transport.


Excitatory input from the colon to the inferior mesenteric ganglion.


A possible histochemical method for the localization of choline acetyltransferase.


The fine structure of avian vascular muscle and its electrical constants obtained with intracellular micro-electrodes.


The effect of adenosine triphosphate on the transmural potential in rat small intestine. 1. ATP either in the mucosal or serosal fluid caused a transient increase in the potential difference and short-circuit current across the wall of rat jejunum in vitro, the serosal solution becoming more positive.2. Similar responses were observed in the ileum and colon, and in in vivo preparations of small intestine.3. The response is relatively specific for ATP.4. The transient nature of the response is not due to rapid hydrolysis of extracellular ATP.5. High concentrations of K(+) in the mucosal medium, serosal ouabain or mucosal 2,4-dinitrophenol all inhibit the response without altering the time course.6. Significant inhibition was not observed in the presence of ADP or in Mg(2+)-free salines.7. The results are consistent with an intracellular action of ATP in the epithelium to stimulate net ion transport. The results do not demonstrate whether or not extracellular ATP can act as an energy donor for an electrogenic ion pump.8. Theophylline prolongs the time course of the response, and the involvement of the adenyl cyclase system cannot be excluded as an explanation for the findings.


Preliminary observations on the application of thermography to the study of brown adipose tissue in the human new-born.


The influence of heart rate on the secretion of a substance closely resembling the 18-monoacetate of D-aldosterone by the hearts of cats under chloralose anaesthesia. 1. A substance (HS), similar to the 18-monoacetyl derivative of D-aldosterone (18 MA) in its physico-chemical and biological properties, is shown to be secreted into the coronary circulation by cat hearts, in vivo.2. The concentrations found in coronary sinus blood from cats resting under chloralose anaesthesia ranged from 20 to 36 ng/ml. equivalent 18 MA activity.3. A positive correlation was found between heart rate and the concentration of HS in coronary sinus blood. This concentration was doubled by a rise in heart rate of 65 +/- 20.2 beats/min when the tachycardia was induced by electrical drive from the right atrial appendage. An increase of only 22.5 +/- 1.76 beats/min doubled the concentration of HS when the acceleration was induced by infusion of adrenaline, noradrenaline or isoprenaline or by atropinization.4. Two methods are described for bio-assay of HS. The reference compound used was 18 MA.


The luteinizing hormone releasing activity of extracts of blood from the hypophysial portal vessels of rats. 1. A method of acid ethanol extraction and gel filtration was used to obtain a ;luteinizing hormone (LH)-free' fraction of blood collected from the cut pituitary stalk of rats (termed hypophysial portal blood).2. The ;LH-free' fraction of hypophysial portal plasma from hypophysectomized and from ovariectomized rats caused a greater depletion of ovarian ascorbic acid in immature rats, pretreated with gonadotrophins, than a similar fraction of systemic plasma obtained from the same donor animals.3. The ;LH-free' fraction of hypophysial portal plasma from ovariectomized rats evoked a rise in the level of LH in the systemic plasma of ovariectomized, oestrogen and progesterone treated, rats. This fraction also caused ovulation in rabbits when infused directly into the anterior pituitary gland of these animals. The activity of the ;LH-free' fraction of systemic plasma was considerably less than that of portal plasma in either of these assay systems.4. The results of these experiments suggest the presence of a factor in the ;LH-free' fraction of hypophysial portal plasma which is capable of causing the release of luteinizing hormone from the anterior pituitary gland. The molecular weight of this factor, as assessed by its behaviour on filtration through ;Sephadex G-25', is probably less than 5000.5. The LRF activity of the ;LH-free' fraction of hypophysial portal plasma obtained from rats at various phases of the oestrous cycle was measured by the ovarian ascorbic acid depletion method. There appears to be a decrease in the level of activity at oestrus. However, a rise in LRF activity, which was expected to occur at the ;critical period' of prooestrus, was not evident. The significance of these findings is discussed.


Luteinizing hormone releasing factor in rat hypophysial portal blood collected during electrical stimulation of the hypothalamus. 1. Ovulation was induced in Nembutal-blocked pro-oestrous rats by electrical stimulation of the hypothalamus.2. The same type of electrical stimulation was applied during the collection of hypophysial portal blood.3. Pooled hypophysial portal plasma from donors in pro-oestrus, oestrus and met-oestrus was assayed for ovarian ascorbic acid depleting (OAAD) activity.4. Electrical stimulation of the hypothalamus increased the OAAD activity, believed to be due to luteinizing hormone releasing factor (LRF), in pro-oestrus and met-oestrus, but not in oestrus.5. It is concluded that the hypothalamic nerve fibres responsible for releasing LRF into the hypophysial portal vessels are depleted of their store of this releasing factor, or are refractory to electrical stimulation, during oestrus.


A thermographic study of the dorsal surface temperature of the new-born rabbit.


The effects of salicylate on temperature regulation in the rabbit. 1. A stable pyrexia has been produced in rabbits by intravenous injection of leucocyte pyrogen followed by a continuous infusion.2. Intravenous sodium salicylate, given 4 hr after the start of pyrogen infusion, induced rapid and progressive defervescence. The rate of fall of temperature was dose dependent.3. Intravenous injection of sodium salicylate had no effect on the temperature of afebrile rabbits.4. The intraventricular injection of small doses of sodium salicylate, given 4 hr after the start of a pyrogen infusion, caused a rapid, dose-dependent defervescence, but had no significant effect on the temperature of afebrile rabbits.5. Salicylates exert at least part of their antipyretic activity through an action on the central nervous system.


Lung volume and mixing efficiency in the new-born infant.


Actions of LSD-25 and reserpine on a serotonergic synapse.


Studies of the effects of dimethothiazine on muscle spindle activity in the decerebrate cat.


Sucrose-gap recording of prolonged electrical activity from arteries in Ca-free solution containing EDTA at low temperature.


An inhibitory effect of prostaglandin E2 on neuromuscular transmission in the guinea-pig vas deferens.


The effect of urethane on transmission along the dorsal column sensory pathway in the rat.


The effects of cortisol on the carbohydrate metabolism of hypophysectomized and of thyroidectomized calves.


Enzymic and physiological studies on normal and disused developing fast and slow cat muscles. 1. Contraction time (CT), (1/2) relaxation time ((1/2) RT), maximum twitch-tetanus tensions and the activity of two glycolytic enzymes (aldolase, pyruvic kinase) and two oxidative enzymes (malic and isocitric dehydrogenase) was studied in anterior tibialis (AT) and soleus (SOL) muscles from birth to 18 weeks of age.2. One hind leg of each of six kittens was casted at birth and the above parameters were examined in both casted and contralateral AT and SOL at 18 weeks of age.3. Differentiation of the contraction properties in normal developing fast muscle (AT) was closely paralleled by a marked elevation in glycolytic enzyme activity. Oxidative enzymic activity in AT and SOL was relatively unchanged from birth to 18 weeks of age, as was glycolytic activity in SOL.4. Disuse, due to immobilization, produced atrophy in AT and SOL muscles at 18 weeks of age. The CT of the casted SOL was slightly quicker than normal while the CT of the AT was unchanged. The glycolytic and oxidative enzymic activity in both casted muscles was generally unchanged but the contralateral AT had higher glycolytic activity than normal muscles.


Effects of a surface active contraceptive agent (nonylphenoxypolyethoxyethanol) on the vagina; a new functional approach to assessing the actions on the vagina of spermicides.


Efferent activity in the lateral line nerve of dogfish.


Early calcium phosphate crystal growth in a solution with some of the properties of serum ultrafiltrate.


Cardiovascular function in young lambs during summit metabolism. 1. Cardiac output in lambs less than 3 days old was 50-100% higher during summit metabolism than during exposure to thermoneutral conditions.2. The Fick method, based on oxygen consumption, and the dye dilution method for determination of cardiac output, gave qualitatively similar results, but there were considerable quantitative discrepancies.3. The thermogenic tissues, muscle and brown fat, extracted some 80% of the oxygen from the blood perfusing them during summit metabolism.4. Significant right to left shunts through the foramen ovale were detected in about half of the lambs during the first few days of life; the size and incidence of shunts decreased with advancing age but were apparently independent of environmental conditions.5. During exposure to extreme cold, left to right shunts through the ductus arteriosus were detected in a high proportion of lambs, < 12 hr old, with detectable foramen ovale shunts. Pressure measurements in pulmonary and systemic arteries in very young lambs indicated that right to left shunting via the ductus was unlikely to occur; none was detected.6. Summit metabolism was poorly related to oxygen carrying capacity of blood, but significant correlations of summit metabolism with cardiac output (positive) and with oxygen saturation of mixed venous blood (negative) were observed, though not consistently.7. It is concluded that the great variability of summit metabolism between lambs older than 6 hr is not readily explained in terms of cardiovascular phenomena, but that the quantity and efficiency of thermogenic tissues probably play an important role in limiting summit metabolism.


Nitrogen washout estimations on new-born infants.


Summit metabolism and cardiovascular function in young lambs during hyperoxia and hypoxia. 1. Exposure of lambs at sea level to air containing more than 33% oxygen resulted in a small increase in summit metabolism (maximum oxygen consumption on severe cold exposure) in some lambs, and in an improvement in the ability to maintain summit metabolism in others; there was a concomitant improvement in the maintenance of cardiac output, but no change in the degree of right to left shunting.2. Hypoxia (12-13% oxygen in inspired air) reduced summit metabolism of new-born lambs by 25%; but there was no effect in lambs 6-11 days old. Hypoxia neither reduced cardiac output, nor affected the degree of right to left shunting.3. The results suggest that in very young lambs there is some limitation of summit metabolism imposed by the supply of either oxygen or substrate to thermogenic tissues.


A technique of perfusion of the isolated canine stomach.


The metabolism of (3H)noradrenaline released by electrical stimulation from the isolated nictitating membrane of the cat and from the vas deferens of the rat. 1. The noradrenaline (NA) stores of the isolated medial muscle of the cat's nictitating membrane were labelled with [(3)H]NA and the tissue was set up in an isolated organ bath for field stimulation. The tritiated NA and its metabolites released spontaneously and by field stimulation were determined by scintillation counting following chromatographic separation.2. NA represented 11.8 +/- 1.0% of the total radioactivity of the spontaneously released tritiated compounds. The rest was accounted for by NA metabolites: (a) normetanephrine (NMN), 35%; (b) 4-hydroxy-3-methoxymandelic acid (VMA), 20%; (c) 3,4-dihydroxyphenylglycol (DOPEG), 10%; (d) 3,4-dihydroxymandelic acid (DOMA), 10%; (e) 4-hydroxy-3-methoxyphenylglycol (MOPEG), 14%.3. Field stimulation at 25 shocks/sec with supramaximal stimuli of 1 msec duration increased the outflow of NA six to eightfold and that of NMN, DOPEG and VMA two to threefold. The increase in outflow of DOMA and MOPEG was small. NA represented 35.8 +/- 4.1% of the total increase in radioactivity.4. After pargyline pretreatment field stimulation increased the outflow of NA and NMN. Stimulation in the presence of pyrogallol raised the release of NA, DOMA and DOPEG. Neither pargyline nor pyrogallol affected the total release induced by stimulation.5. Cocaine 0.3 mug/ml. increased the release due to stimulation at 4 shocks/sec but not at 25 shocks/sec. Cocaine did not affect the metabolism of the released transmitter.6. Phenoxybenzamine (10 mug/ml.) increased release by stimulation at 4 and 25 shocks/sec. Metabolism of the released transmitter was prevented in the presence of phenoxybenzamine.7. Phentolamine (3 mug/ml.), like phenoxybenzamine, blocked responses to field stimulation, but failed to modify release and subsequent metabolism of NA liberated by field stimulation.8. The main NA metabolites in the rat vas deferens were DOPEG, DOMA and MOPEG. Stimulation at 4 shocks/sec resulted in an increased outflow of NA and of DOPEG. Fifty per cent of the total increase of radioactive compounds was accounted for by NA metabolites.9. These experiments show that for the calculation of the actual output of transmitter it is important to include the metabolites and not to rely on the determination of [(3)H]NA alone.


The relation between carotid body chemoreceptor discharge, carotid sinus pressure and carotid body venous flow. 1. Activity in forty-two single chemoreceptor afferent fibres from the carotid body in thirty-nine cats was measured when the carotid body was naturally and artificially perfused. In nine of these cats, carotid body venous flow was also measured.2. When pressure within the carotid sinus segment was suddenly raised or lowered, chemoreceptor activity changed in the opposite direction within the first 5-10 sec by an amount which was significantly greater than the variation of activity in the control period. Thereafter activity stabilized at a level which was not different from control.3. Whether the carotid body was naturally or artificially perfused, carotid body chemoreceptor activity, following this initial transient change, was unaffected in eight out of twelve fibres by alterations in carotid sinus pressure within the range 60-160 mm Hg and carotid body venous flow 10-60 mul./min, blood gas tensions and pH being maintained constant. In the four remaining fibres, chemoreceptor activity increased slightly but significantly as pressure was lowered in this range. Chemoreceptor activity increased in all fibres tested when pressure was lowered below 50-60 mm Hg.4. Chemoreceptor response curves to changes in P(a,O2) (30-450 mm Hg), P(a,CO2) (27-62 mm Hg) or [H(+)](a) (3-7 x 10(-5) m-equiv/l.) were not significantly different whether the carotid body was perfused (a) naturally at the prevalent systemic pressure, (b) artificially at the same pressure, or (c) artificially at one higher pressure, 130 or 140 mm Hg.5. These results indicate that the carotid body chemoreceptors are relatively unaffected by sustained changes in arterial pressure or in total carotid body flow within the physiological range.


Observations on coronary collateral communications and the control of flow in the coronary circulation of the dog. 1. Pressure was measured in the small arterial anastomosing branches of the coronary vascular network. The mean value was 30 mm Hg not significantly different from the mean value of 33 mm Hg for peripheral coronary pressure measured distal to a ligature on the anterior descending branch of the left coronary artery. Evidence was adduced to show that either the anterior descending or the circumflex artery had the capacity to maintain network pressure at levels adequate for tissue perfusion.2. The network has both capacity and compliance. Filling of the network compliance during systole probably accounts for the systolic phase of coronary flow. Flow through the microcirculation is probably entirely diastolic, the combined compliance of the aorta and large vessels together with the network provides the necessary reservoir, the potential energy indicated by diastolic pressure provides the perfusion pressure head.3. Resistance of vessels between the aorta and network cannula (pre-net) was approximately double that of the microcirculation (post-net). The smaller pre-network vessels are of the order 70 mum in diameter. Both pre- and post-network vessels are vaso-active and respond similarly to adrenaline and haemorrhage.


Rigor contraction and the effect of various phosphate compounds on glycerinated insect flight and vertebrate muscle. 1. Glycerol-extracted flight muscle from the giant water-bug, Lethocerus cordofanus, undergoes contraction when deprived of ATP. This rigor contraction occurs in the presence of the calcium chelating agent EGTA, under conditions in which the predicted free calcium ion concentration is less than 5 x 10(-9)M. A mechanically similar contraction has been observed by depriving the muscle of Mg(2+), in the presence of 5 mM-ATP.2. In the rigor contraction tensions of up to 120 mN/mm(2) under isometric conditions, and shortenings of between 2(1/2) and 6% under isotonic conditions, have been observed at 20 degrees C.3. Muscles in rigor can be relaxed by the addition of ATP. The minimum concentration of ATP required to give full relaxation depends upon other ionic constituents of the solutions, and upon temperature, but is between 0.3 and 1 mM at 20 degrees C. Lower concentrations result in partial reduction of tension and stiffness.4. Pyrophosphate (PP) causes a reduction in the tension of muscle which has developed rigor under isometric conditions, but the stiffness, when measured at frequencies between 1 and 100 Hz, remains indistinguishable from that of rigor muscle. The stiffness when measured by applying slow length changes is comparable to that of ATP-relaxed muscle. It is suggested that in PP-relaxed muscle the cross-bridges remain in close proximity to, but are not rigidly attached to, the I filaments, resulting in a high viscous interaction between the two sets of filaments.5. The addition of low concentrations of ADP (less than about 0.7 mM) to rigor muscle in the absence of ATP causes an increase in tension. The effect is sigmoid, and is probably due to the formation of low concentrations of ATP throughout the body of the fibre by myokinase activity. Larger concentrations of ADP (about 5 mM) added to rigor muscle cause relaxation, probably due to the formation of higher ATP concentrations.6. AMP and inorganic orthophosphate have little effect upon the mechanical properties of rigor muscle.7. There is a delay of about 1 min before the onset of rigor contraction when fibres are transferred from an ATP-solution to one containing no ATP, due to the transfer of ATP in the body of the fibres. Both ATP hydrolysis by the fibres and diffusion of ATP into the bathing solution contribute significantly to the rate of depletion of ATP.8. Rabbit psoas muscle shows a similar rigor contraction in the presence of EGTA, and has mechanical properties similar to those described for Lethocerus flight muscle in the presence of pyrophosphate.


Voltage clamp experiments in striated muscle fibres. 1. Membrane currents during step depolarizations were determined by a method in which three electrodes were inserted near the end of a fibre in the frog's sartorius muscle. The theoretical basis and limitations of the method are discussed.2. Measurements of the membrane capacity (C(M)) and resting resistance (R(M)) derived from the current during a step change in membrane potential are consistent with values found by other methods.3. In fibres made mechanically inactive with hypertonic solutions (Ringer solution plus 350 mM sucrose) step depolarizations produced ionic currents which resembled those of nerve in showing (a) an early transient inward current, abolished by tetrodotoxin, which reversed when the depolarization was carried beyond an internal potential of about +20 mV, (b) a delayed outward current, with a linear instantaneous current-voltage relation, and a mean equilibrium potential with a normal potassium concentration (2.5 mM) of -85 mV.4. The reversal potential for the early current appears to be consistent with the sodium equilibrium potential expected in hypertonic solutions.5. The variation of the equilibrium potential for the delayed current (V'(K)) with external potassium concentration suggests that the channel for delayed current has a ratio of potassium to sodium permeability of 30:1; this is less than the resting membrane where the ratio appears to be 100:1. V'(K) corresponds well with the membrane potential at the beginning of the negative after-potential observed under similar conditions.6. The variation of V'(K) with the amount of current which has passed through the delayed channel suggests that potassium ions accumulate in a space of between (1/3) and (1/6) of the fibre volume. If potassium accumulates in the transverse tubular system (T system) much greater variation in V'(K) would be expected.7. The delayed current is not maintained but is inactivated like the early current. The inactivation is approximately exponential with a time constant of 0.5 to 1 sec at 20 degrees C. The steady-state inactivation of the potassium current is similar to that for the sodium current, but its voltage dependence is less steep and the potential for half inactivation is 20 mV rate more positive.8. Reconstructions of ionic currents were made in terms of the parameters (m, n, h) of the Hodgkin-Huxley model for the squid axon, using constants which showed a similar dependence on voltage.9. Propagated action potentials and conduction velocities were computed for various conditions on the assumption that the T system behaves as if it were a series resistance and capacity in parallel with surface capacity and the channels for sodium, potassium and leak current. There was reasonable agreement with observed values, the main difference being that the calculated velocities and rates of rise were somewhat less than those observed experimentally.


Slow changes in potassium permeability in skeletal muscle. 1. Voltage clamp experiments on sartorius muscle fibres at 3 degrees C showed that the potassium current is divisible into three components, namely:(a) Current in the delayed rectifier channel, which reached a maximum in about 0.1 sec at -30 mV, and declined with a time constant of about 4 msec when the fibre was repolarized to -100 mV; this component had an approximately linear instantaneous current-voltage relation and an equilibrium potential E(1) at 10-15 mV positive to the resting potential.(b) A slow component which reached a maximum in about 3 sec at -30 mV, and declined with a time constant of about 0.5 sec when the fibre was repolarized to -100 mV; this component had an approximately linear instantaneous current-voltage relation and a mean equilibrium potential E(2) at -83 mV in fibres where E(1) averaged -75 mV.(c) Current in the inward rectifier channel which decreased with a time constant of about 0.25 sec when the fibre was hyperpolarized to -150 mV. This component had an equilibrium potential close to the resting potential and an instantaneous current-voltage relation which was that of an inward rectifier.2. The general characteristics of the late after-potential in muscles in hypertonic solutions at 3 degrees C are consistent with those of the slow conductance change. The sign of the late after-potentials was reversed by depolarizing below -80 mV.3. The decline of current during a maintained hyperpolarization cannot be attributed solely to a decrease in tubular potassium concentration, since there may be a large decrease in current without much alteration of equilibrium potential. The negative slope conductance often seen at -150 mV is also difficult to reconcile with the tubular depletion hypothesis.4. Replacement of 10 mM-K by 10 mM-Rb abolished inward rectification but had less effect on the fast and slow components of the potassium conductance.


interactions between histamine and bradykinin assessed by continuous recording of increased vascular permeability. 1. The responses of the cutaneous blood vessels of the guinea-pig to histamine and bradykinin have been studied in order to determine whether these factors mediate vascular changes by acting on different blood vessel receptors.2. In animals injected intravenously with bovine serum albumin labelled with phosphorus (32)P the reactions to histamine and bradykinin have been studied by continuously recording the local radioactive emission from the skin.3. Histamine increased the intensity of radioactive emission for 7-15 min. The level of radioactivity then remained almost constant for at least 1 hr. Bradykinin increased the rate of emission for 5-7 min but the radioactivity decreased by approx. 30% in 1 hr.4. The intensity of the response to histamine was markedly diminished in sites previously treated with either histamine or bradykinin, compared with the reaction in normal skin. However, a response of similar intensity to that in normal skin was evoked by histamine earlier in sites previously treated with bradykinin than in sites treated with histamine. By contrast, bradykinin evoked a similar reaction to that in normal skin, in sites previously treated with either histamine or bradykinin.5. The dissimilarity of the responses evoked by histamine and bradykinin suggests that there are two types of blood vessel receptors. One type may be activated by both histamine and bradykinin but becomes refractory to further stimulation with histamine. The other type of receptor is activated only by bradykinin and does not become refractory.


Gallamine triethiodide (flaxedil) and cat retinal ganglion cell responses. 1. Repeated flashes of diffuse light were presented to the cat's eye over long periods of time (hours) while the mixed ganglion cell response was recorded from single axons in the optic tract. This was done for cats receiving gallamine triethiodide intravenously and for cats who did not receive the drug.2. All responses were transformed into instantaneous pulse density tracings. Such tracings from control and gallamine cells were compared to observe possible effects of gallamine: (a) the shape (time course) did not change during gallamine administration; (b) maximum firing frequency, total number of spikes and latency was measured for both the on- and the off-component on the pulse density tracings and plotted versus time. Statistical methods failed to reveal any difference between the manner in which these response features of control cells and of gallamine cells varied with time.


Caudate nucleus neurones: correlation of the effects of substantia nigra stimulaton with iontophoretic dopamine. 1. Extracellular recordings were made from caudate nucleus neurones in decerebrate cats using five-barrel micropipette electrodes.2. Electrical stimulation of the substantia nigra caused spike rate depressions in 121 of 260 caudate neurones as evidenced by changes in the post-stimulus histograms of their firing patterns. Spike rate facilitation occurred with forty-two caudate units.3. Neurones depressed by nigral stimuli were consistently depressed by micro-iontophoretic dopamine.4. Alpha-methyldopamine, administered iontophoretically, antagonized the depressant responses induced by both nigral stimulation and iontophoretic dopamine.5. The data are compatible with the concept that the caudate neuronal depressant responses produced by nigral stimulation are mediated by a direct dopaminergic nigro-neostriatal pathway. The possibility of mediation via polysynaptic pathways cannot, however, be completely excluded.


The effect of temperature in the range 0-35 degrees C on the resting tension of frog's muscle. 1. It has long been known that a resting muscle shows a reversible ;rubber-like' response to a change of temperature: it develops tension when warmed and this reverses on cooling. It was recently shown (Hill, 1968) that part of the resting tension is due to a weak interaction between the sliding filaments, and it was suggested that the rubber-like tension might be caused by the same process rather than by some inert structural component. Further information on this point has now been obtained from some observations on the effect of temperature on isometric tension at temperatures not far below the level (28-35 degrees C) at which a heat contracture is produced.2. The temperature of a frog's sartorius was changed by moving it up and down in a vessel containing Ringer solution at two different temperatures. The temperature in one part was maintained constant in the range 0-20 degrees C and in the other at 5-35 degrees C. The changes was 90% complete in 12 sec.3. From 0 degrees up to about 23 degrees C the tension developed per 1 degrees C rise of temperature (DeltaP/DeltaT) is almost constant, but as the temperature approaches the level at which a heat contracture appears the value of DeltaP/DeltaT rises steeply. This behaviour indicates that the tension in question has an ;active' rather than a ;passive' origin, and this view is supported by other evidence from experiments with muscles in hypertonic solutions, described in the next paper.4. It was found that the temperature at which a muscle goes into a heat contracture depends on the length at which it is set; the critical temperature is lower in an extended muscle. A shortened muscle at a temperature not far below the critical value will therefore produce a contracture when it is stretched.


Effects of fasting on intestinal transfer of sugars and amino acids in vitro. 1. Transfer of sugars, amino acids and fluid and metabolism of glucose were studied with everted sacs of small intestine prepared from fed and 3-day fasted rats.2. In the absence of glucose there was some evidence for increased intestinal transfer of sugars and amino acids in fasted animals. In the presence of glucose there was in general decrease in transfer of amino acids and fluid.3. In fasted animals glucose transfer was reduced except in the lower ileum, and there was a general reduction in glucose metabolism.4. Because of the large reduction in gut weight in fasted animals, expressing transfer on a weight basis is considered not to be a valid procedure in studying the effects of fasting on intestinal transfer.5. The results have been discussed in relation to effects of fasting on energy availability, efficiency of transfer mechanisms, permeability of the intestine and the value of in vitro methods in the study of physiological absorption.


The effect of temperature on the resting tension of frog's muscle in hypertonic solutions. 1. It has long been known that the tension of a resting muscle rises when it is warmed and falls on cooling. It is shown here that treatment with hypertonic solution causes an alteration in this effect; the usual rise or fall of tension with warming or cooling is then preceded by a transient change in the opposite direction.2. The magnitude of the abnormal reversed phase does not depend in a simple, linear, manner on the temperature change. For instance, the effect for cooling from 20 to 0 degrees C is much greater than twice that for 10 to 0 degrees C.3. The results lead to the suggestion that the tension, in both normal and hypertonic muscle, comes from an active process. It is proposed that a temperature change operates by altering the concentration of an ;activating substance', and that the change of concentration becomes delayed by hypertonicity.


The afferent innervation of two infrahyoid muscles of the cat. 1. The afferent innervation of the straplike muscles of the infrahyoid region were investigated in two ways. The morphology of spindles and counts of tendon organs were investigated by the gold chloride technique in ten muscles. Spindle counts were made in forty pairs of thyrohyoid and infrahyoid muscles. De-efferenting of the nerves to these muscles was done in three cats and the calibre spectra of the afferent innervation investigated. These were compared with the total counts of fibres in intact nerves.2. In the thyrohyoid, spindles are frequently absent. No tendon organs were seen. In the large infrahyoid (combined sternohyoid and sternothyroid), spindle counts varied from 0 to 20 and the mean spindle count per gram of muscle was 3.5. A maximum of five tendon organs were seen in the muscle. Both spindle and tendon organ counts are low when compared with a limb muscle of similar weight and size.3. In the infrahyoid muscle complex spindles were about equal in number to simple spindles.4. Counts of spindles in the infrahyoid muscle in families of three or more siblings suggest that some families of kittens tend to have higher spindle counts than other families.5. The afferent innervation of the two muscles varied between 21 and 42% of the total fibre population and the fibre diameter spectrum is in keeping with the low counts of encapsulated endings.


The effect of noradrenaline on the toad skin potential. 1. The electrical response of isolated toad skins to the presence of 4 x 10(-5)M noradrenaline in the inner medium has been studied.2. When skins were bathed in Ringer solution, noradrenaline initiated a partial depolarization of the skin potential (inside surface becoming less positive) followed by a hyperpolarization; however, noradrenaline depolarized skins in sulphate Ringer.3. The origin of the hyperpolarizing phase of the response to noradrenaline was studied by comparing the size of perturbations in the skin potential, produced by identical changes in external sodium, external chloride or internal potassium concentrations, before and during the response to noradrenaline.4. Measurements of skin conductance were made in different sulphate media in order to estimate the magnitudes of the conductance of the shunt pathway through the skin and the conductance of the pathway for actively transported sodium ions.5. Interpretation of both the variations in the perturbations of skin potential and the skin conductance measurements led to the conclusion that the hyperpolarizing phase of the response to noradrenaline was generated by an increase in the sodium to chloride permeability ratio for the outer barrier. It was considered that other evidence was compatible with this view.6. Similar experimental methods were employed to study the action of antidiuretic hormone (ADH) and an elevated external concentration of calcium on the outer barrier. It was found that ADH increased the sodium to chloride permeability ratio whereas calcium decreased it. The separate actions of ADH and calcium on the sodium permeability of the outer barrier did not interfere apparently with the subsequent ability of noradrenaline to increase the sodium to chloride permeability ratio for this barrier in the skin.


Daily changes in foetal and maternal blood of conscious pregnant ewes, with catheters in umbilical and uterine vessels. 1. Blood gas tensions, pH, packed cell volume (PCV) and the levels of glucose, fructose and lactic acid have been followed in foetal and maternal blood for periods of 3-30 days in conscious ewes between 80 days gestation and term ( approximately 147 days).2. Blood samples were withdrawn through indwelling catheters placed in one or both umbilical vessels, a uterine vein and a maternal artery.3. The success of the operation appeared to depend on the maintenance of maternal blood gas and pH levels within normal limits as well as on the final position of the tip of the catheter. The difficulties and limitations of the technique are discussed.4. Foetal blood gas tensions, pH, PCV, lactic acid and glucose levels did not change markedly during the last 50-60 days of gestation. The fructose concentration fell during this period, the greatest change was between 100 and 120 days gestation.5. Small fluctuations in P(O2), P(CO2) and pH in umbilical venous blood were associated with similar changes in the uterine vein, so that the gradients across the placenta appeared to remain constant.6. Daily changes in maternal plasma glucose levels were reflected in similar changes in foetal plasma fructose and by much smaller alterations in the foetal glucose levels. The glucose concentration in the foetal plasma was less than 25% of that in maternal plasma.7. The existence of a general relationship between maternal plasma glucose and foetal plasma fructose was masked by the independent fall in fructose levels with age. However, at any given stage of gestation, there was a significant correlation between foetal fructose and maternal glucose.8. Few changes in the umbilical blood were associated with impending abortion or birth. Blood gas tensions remained constant, but a sharp fall in fructose levels often occurred 48 hr before any changes in pH, PCV and lactate concentration.9. Present and other findings on conscious animals are compared with previous observations on acute, anaesthetized preparations.


PO2, PCO2 and pH levels in the umbilical and uterine blood of the mare and ewe. 1. Foetal and maternal blood gas tensions and pH levels have been investigated in the mare and the ewe during late pregnancy under a number of experimental conditions.2. Observations were made on anaesthetized animals with the foetus in utero. Simultaneous blood samples were withdrawn from a maternal artery and uterine vein, and from the two umbilical vessels, through catheters inserted at the beginning of each experiment.3. At normal maternal arterial P(O2) (80-110 mm Hg) the umbilical venous P(O2) of the foal was very high (49 mm Hg) and the P(O2) in the umbilical artery (33 mm Hg) was similar to that in the umbilical vein of the lamb (34 mm Hg).4. The P(O2) difference between the umbilical and uterine venous blood was 17 mm Hg in the ewe but only 4 mm Hg in the mare. The corresponding P(CO2) gradients were about one quarter of those for oxygen in both species.5. When the maternal arterial P(O2) was raised above 100 mm Hg both uterine venous and umbilical P(O2) increased in the mare, and the gradient between the uterine vein and umbilical vein was reversed, whereas little change occurred in the corresponding vessels of the ewe.6. Alterations in maternal arterial P(CO2) were associated with concomitant changes in the blood in the other three vessels but in both species the P(CO2) difference between uterine and umbilical venous blood appeared to remain constant.7. Foetal blood pH levels followed those of the mother if the changes in the maternal blood were of respiratory origin. The effects of prolonged changes in maternal pH on foetal levels were investigated in the ewe. Foetal pH remained unchanged during maternal alkalaemia (pH 7.7) induced by Na(2)CO(3) infusions, but increased during a similar rise in maternal pH induced by hyperventilation.8. The present observations have been compared with findings on the conscious animal and possible explanations for the differences between the two species are discussed.


Physiological and morphological properties of motoneurones in the central nervous system of the leech. 1. A number of motor cell bodies have been identified in the segmental ganglia of the ventral nerve cord of the medicinal leech. These motoneurones supply either excitatory or inhibitory innervation to the muscles in the body wall.2. Several tests were made to establish that each of the identified motoneurones directly innervates muscle fibres. (a) By injecting a fluorescent dye into the cell bodies of motoneurones, their axons were traced through one or both contralateral roots. (b) Electrical stimulation of a motoneurone by an intracellular electrode caused a single nerve impulse to travel through the roots to the muscles where it set up an excitatory or an inhibitory junctional potential. (c) Impulses set up in the roots were conducted antidromically to the cell body. (d) If the preparation was bathed in 20 mM-Mg(2+), which blocks chemical synapses, conduction from the cell body to the muscles was not interrupted. Thus it is unlikely that an interneurone was interposed in the pathway within the ganglion.3. Fourteen pairs of excitatory cells and three pairs of inhibitory cells can be identified in each of the twenty-one segmental ganglia. These neurones together supply the five different muscle layers in each segment which execute the movements of the leech. Each neurone innervates a territory of muscle fibres which has a consistent size and location from segment to segment. Several lines of evidence suggest that the identified cells form a major fraction of the total number of excitatory motoneurones in the ganglion.4. The territories of the motoneurones are arranged in a quilt-like pattern closely resembling that already found for the receptive fields of sensory cells on the skin. Within the longitudinal muscle sheet, individual cells supply narrow or wide strips. The firing of each cell thus could produce bending of the segment in various directions or symmetrical shortening of it, depending on which of the motoneurones were active.5. It is possible to deduce which motoneurones are firing to produce a particular movement of the animal. Thus these experiments provide a basis for studying reflex integration between motoneurones and the identified mechanosensory cells in the ganglion.


Intrapulmonary receptor response to changes in airway-gas composition in Gallus domesticus. 1. A unidirectional, artificial ventilating system was used to observe respiratory and neural responses to changes in CO(2) concentration in pulmonary airways of the chicken.2. Sectioning any of the three pulmonary branches of the vagus slowed the respiratory response to sudden removal of CO(2) from unidirectional ventilating gas stream.3. The impulse frequency of CO(2)-sensitive units was inversely related to the CO(2) content in the ventilating gas stream.4. Abrupt elimination of CO(2) from the ventilatory gas stream caused a transient burst of activity from CO(2)-sensitive receptors, which quickly adapted to a constant discharge frequency. Fifty percent of the units responded within 0.35 sec after CO(2)-free gas reached the lungs. The neural response to abrupt re-addition of CO(2) to the gas stream was less rapid.5. Acetylcholine or NaCN injected into the pulmonary artery had no apparent effect on the discharge of CO(2)-sensitive receptors. Veratridine temporarily reduced discharge and occasionally produced short, rapid bursts of activity.6. Hypoxia and hyperoxia (5% and 80% O(2)) produced no significant change in the discharge of CO(2)-sensitive receptors.7. Carbon dioxide-sensitive units in spontaneously breathing chickens were silenced by adding 10% CO(2) to the inspired gas; the units responded vigorously to inflation of the respiratory system with a gas containing no CO(2) but remained silent during inflation with gas containing 15% CO(2). Units insensitive to CO(2), which increased their impulse frequency during inflation regardless of the CO(2) content of the inflating gas, also were observed.


Monosynaptic chemical and electrical connexions between sensory and motor cells in the central nervous system of the leech. The synaptic connexions that underlie three different segmental shortening reflexes have been traced by recording intracellularly from individual sensory and motor nerve cells in the C.N.S. of the leech. The fourteen sensory cells involved in these reflexes respond specifically to one of three modalities: touch, pressure, or noxious stimuli applied to the skin. All three types of sensory neurone give rise to excitatory synaptic potentials in two large motoneurones. Each of these motor cells provides excitatory innervation to the longitudinal muscle fibres of the opposite side of the segment. The mechanism of synaptic transmission is, however, different for each type of sensory cell.1. An impulse in a sensory cell that responds to touch gives rise to a short-latency depolarizing potential in the large longitudinal motoneurones by way of an electrical synapse. This junction rectifies so that excitation can spread in only one direction (from the sensory to the motor cell), whereas a hyperpolarizing potential can pass only in the opposite direction.2. The synaptic potential evoked in the motoneurone by an action potential in a sensory cell responding to noxious stimuli can be attributed to the action of a chemical transmitter agent and has different properties: the post-synaptic potential arises after a delay of about 2-4 msec, is abolished by high concentrations of Mg, and enhanced by high concentrations of Ca. Several lines of evidence show that this connexion is monosynaptic.3. The synaptic potential following an impulse in a pressure cell is produced by both chemical and electrical synaptic mechanisms. Rectification, similar to that described for the touch cell, also occurs at this electrical synapse.4. One or more impulses in any one of the fourteen mechanoreceptor cells in the ganglion can initiate impulses in the large longitudinal motoneurones to produce a shortening of the segment. The contraction is abolished by blocking impulse initiation in the motoneurones.5. The arborizations of the sensory cells and the motoneurone within the neuropile have been studied histologically after injecting a fluorescent dye. Their processes are intertwined in a highly complex manner so that the sites of the synaptic junctions cannot be determined with the resolutions so far achieved. Nevertheless, taken together the histological and the electrical results support the idea that individual cells are connected in a stereotyped pattern and operate by distinctive mechanisms.6. These findings provide a basis for studying the functional role of chemical and electrical synaptic mechanisms in these pathways.


Structural changes in the small intestine associated with the uptake of polyvinyl pyrrolidone by the young ferret, rabbit, guinea-pig, cat and chicken. 1. The entry of [(125)I]polyvinyl pyrrolidone (PVP) of mean mol. wt. 160,000 (K. 60) into the epithelial cells of the small intestine has been measured in new-born animals of five species.2. The distribution along the intestine of cells capable of taking up [(125)I]PVP and the decrease and eventual cessation of uptake (closure) with increasing age have been investigated, and have been related to changes in the histological appearance of the small intestine.3. The small intestine of the ferret took up PVP readily until 33-34 days after birth. From 34 to 37 days of age PVP uptake declined sharply and disappeared completely by 40-45 days.4. In the ferret, unlike other species studied, some PVP was taken up by the duodenum. This continued for the first 4 weeks after birth. Thereafter PVP uptake gradually became confined to the terminal ileum.5. In the guinea-pig, PVP uptake was limited to the first 48 hr after birth. During this period the site of uptake was progressively restricted to the terminal ileum.6. In the rabbit, PVP could be taken up in the distal two-thirds of the small intestine for at least 20 days after birth. A decline in uptake occurred between 20 and 22 days after birth in most animals.7. Wide individual variations were seen in the kitten, but PVP uptake was seen in some animals up to 14 days after birth.8. Newly hatched chicks and chicks tested 48 hr after hatching did not take up PVP.9. Histological examination of the small intestine with the light microscope demonstrated that in all species PVP uptake was associated with the presence of vacuoles in the epithelial cells of the villus.10. In the young guinea-pig, large PAS-positive granules were seen in the macrophages of the lamina propria. These appeared to migrate through the epithelium into the intestinal lumen. The significance of this finding and its relation to macromolecular uptake remain unclear.


The effect of procaine on neuromuscular transmission. 1. The mechanism of procaine action on post-synaptic receptors for acetylcholine was studied by recording the end-plate current at membrane potentials ranging from about +30 to about -140 mV.2. It has been found that at resting membrane potential of about -60 to -80 mV the end-plate current has a fast initial and a slow late component. During hyperpolarization of the muscle fibre the amplitude of the slow component is depressed and its half-time lengthened. When the membrane potential is inverted the difference in the time course of both components is much less pronounced or absent.3. It is suggested that procaine modifies the receptor response induced by acetylcholine, and that this modification is dependent on membrane potential.


Neuromuscular transmission in new-born rats. 1. End-plate potentials (e.p.p.s) were recorded intracellularly from the isolated phrenic/diaphragm preparation of the rat during the first few weeks of life.2. Most e.p.p.s at birth were complex and resulted from the summation of two to four units, which could be separated by their different latencies and thresholds to stimulation of the phrenic nerve.3. The e.p.p.s became simpler during the second week of the rats' life, and by 16-18 days old the e.p.p.s consisted of single units, and resembled the e.p.p.s of adult rat muscle.4. It is proposed that the units of the e.p.p. resulted from the stimulation of separate nerve axons and that all but one of the synapses on each muscle fibre were lost during the second week of life.


The proprioceptive reflex control of the intercostal muscles during their voluntary activation. 1. A quantitative study has been made of the reflex effects of sudden changes in mechanical load on contracting human intercostal muscles during willed breathing movements involving the chest wall. Averaging techniques were applied to recordings of electromyogram (EMG) and lung volume, and to other parameters of breathing.2. Load changes were effected for brief periods (10-150 msec) at any predetermined lung volume by sudden connexion of the airway to a pressure source variable between +/- 80 cm H(2)O so that respiratory movement could be either assisted or opposed. In some experiments airway resistance was suddenly reduced by porting from a high to a low resistance external airway.3. Contracting inspiratory and expiratory intercostal muscles showed a ;silent period' with unloading which is attributed to the sudden withdrawal from intercostal motoneurones of monosynaptic excitation of muscle spindle origin.4. For both inspiratory and expiratory intercostal muscles the typical immediate effect of an increase in load was an inhibitory response (IR) with a latency of about 22 msec followed by an excitatory response (ER) with a latency of 50-60 msec.5. It was established using brief duration stimuli (< 40 msec) that the IR depended on mechanical events associated with the onset of stimulation, whereas stimuli greater than 40 msec in duration were required to evoke the ER.6. For constant expiratory flow rate and a constant load, the ER of expiratory intercostal muscles increased as lung volume decreased within the limits set by maximal activation of the motoneurone pool as residual volume was approached.7. The ER to a constant load increased directly with the expiratory flow rate at which the load applied, also within limits set by maximal activation of the motoneurone pool.8. For a given load, the ER during phonation was greater than that occurring at a similar expiratory flow rate without phonation when the resistance of the phonating larynx was mimicked by an external airway resistance.9. It is argued that the IR is due to autogenetic inhibition arising from tendon organs and that the ER is due to autogenetic excitation arising from intercostal muscle spindles.10. The initial dominance of inhibition in this dual proprioceptive reflex control was not predicted by the servo theory. It is proposed that the reflex pathways subserving autogenetic inhibition are under a centrifugal control which determines in relation to previous experience (learning) the conditions under which autogenetic facilitation is allowed.


Medullary activation of intercostal fusimotor and alpha motoneurones. 1. Studies have been made of the anatomical localization in the brain stem of the sites at which tetanic stimulation evoke inspiratory and expiratory apneusis.2. The inspiratory responses arise from a relatively circumscribed region within the medulla corresponding to the nucleus reticularis giganto-cellularis and ventralis which give rise to the medullary contingent of the long reticulo-spinal tracts. Expiratory responses were obtained dorsal and lateral to this area, but not localized to any cyto-architectonically distinct region of the reticular formation.3. During the apneustic responses there was co-activation of the intercostal alpha and fusimotor neurones with reciprocal inhibition of the antagonistic motoneurones. The threshold for activation of the fusimotor neurones was usually lower than for the alpha motoneurones.4. Results with brief tetanic stimulation suggest that the long reticulospinal tracts are responsible for the apneustic responses and that the effects are mediated at segmental level over an interneuronal pathway.5. The response of the intercostal motoneurones during the apneustic responses is shown to be dependent on the integrity of the dorsal spinal roots.


Adrenaline in bird brain.

Adrenaline in bird brain. 1. Catecholamine estimations were made on the whole diencephalon and on the hypothalamus of pigeons and fowls using fluorimetry of the acetylated amines as one, and bio-assay after chromatographic separation of the amines as a second method.2. There was no significant difference between the results obtained by the two methods; for pigeons mean percentage methylation was 10% with one and 12% with the other technique, and in the Rhode Island Red breed of fowls the corresponding figures were 28 and 31%.3. The percentage methylation for the hypothalamus of another breed of fowls (Plymouth Rock) was the same as in Rhode Island Red, but it was significantly lower in White Leghorn birds.4. Between the ages of 3.5 weeks and maturity the percent methylation remained unchanged.5. There is no evidence to suggest that bio-assay of adrenaline as used in this and previous work lacks specificity, but differences between avian breeds exist and have to be reckoned with.


Rubidium, sodium and ouabain interactions on the influx of rubidium in rat red blood cells. 1. The activation curve of rubidium influx by external rubidium in rat red cells showed an inflexion at a concentration around 0.2 mM. This inflexion point was displaced to the right by ouabain.2. The removal of sodium from the external solution changed the characteristics of the activation curve of rubidium influx. At external rubidium below 0.5 mM the uptake increased whereas above that concentration there was marked reduction. Thus the sodium-free effect on rubidium uptake is dependent on the external rubidium concentration.3. With 0.25 mM rubidium, the relationship between increase of rubidium influx and reduction of external sodium followed a more or less exponential function. All the increment was ouabain-sensitive.4. With a rubidium concentration above 0.5 mM the reduction of the rubidium uptake, as sodium was removed, followed curves of complex shape. With 10 mM rubidium, when sodium was reduced from 5 mM to zero, there was an increase instead of a further reduction. These results suggest interactions of several effects.5. The ouabain sensitivity of the rubidium influx in rat red cells is smaller than in other systems studied up to now. The dose-response curve was shifted to the right as the rubidium concentration increased and a plateau was obtained with rubidium only below 1 mM at 10(-5)M ouabain. When plotted as a percentage of the maximal inhibition the points fell into the theoretical curve following a simple one reactant/one site reaction.6. Ouabain inhibition seems to be a complex function of at least three variables: the concentration of the glycoside, the concentration of sodium and the concentration of rubidium. When sodium was absent, 10 muM rubidium was able to prevent, to a great extent, the inhibition produced by 10(-5) and 10(-4)M ouabain.


Dependence of acetylcholine desensitization on the membrane potential of frog muscle fibre and on the ionic changes in the medium. 1. The rate of desensitization of the post-synaptic membrane to prolonged action of acetylcholine was investigated during (a) potassium depolarization of the frog muscle fibre, (b) artificial changes of the membrane potential and (c) in the presence of some multivalent cations and of caffeine.2. Depolarization of the muscle fibre by 15 mM-K(+) led to a slowing down in the development of desensitization by 80%. This effect on desensitization produced by membrane potential changes could account for the previously described effect of increased K(+) concentration.3. Electrotonically produced depolarization of the muscle fibre membrane resulted in a decrease, hyperpolarization in an increase of the rate of desensitization.4. Several multivalent cations can be, according to their ability to increase rate of desensitization, arranged in the following series: [Formula: see text]5. Caffeine in a concentration of 1.5 mM does not affect the rate of desensitization.6. A hypothesis is presented suggesting that desensitization is not only restricted to the receptor level but that it also occurs, at least partly, at the terminal stages of the activation system.


The effect of changes in lung volume on the size and shape of alveoli. 1. A technique is described by which living anaesthetized guinea-pigs were artificially ventilated with a positive and negative pressure cycle, and rapidly frozen at the instant of cessation of ventilation at a preselected point on the respiratory cycle.2. The dimensions of alveoli and alveolar ducts were measured by histological morphometric methods, and related to the degree of lung inflation at the instant of freezing.3. The alveolar volume fraction increased from 0.52 at low lung volumes, up to 0.62 at lung volumes in the mid-inflation range, then decreased to 0.51 at high lung volumes. The alveolar duct volumetric fraction remained constant at all lung volumes.4. The total volume of alveoli increased linearly with increase in lung volume. The total alveolar duct volume increased little until the lungs were 40% inflated, above which it increased steeply.5. The total number of alveoli was linearly related to the body weight.6. The total alveolar surface area increased steeply between lungs of low lung volume and those which were up to 50% inflated, above which the increase levelled off. The absolute values of total alveolar surface depended on the body weight as well as the degree of lung inflation.7. The mean alveolar duct diameter was 40% greater, and the mean alveolar mouth diameter 35% greater in lungs which were fully inflated than in lungs which were nearly collapsed. The average geometrical shape of alveoli was not related to the degree of lung inflation.8. The harmonic mean thickness of the air-blood barrier was 33% less in lungs which were fully inflated than in lungs which were nearly collapsed. The alveolar surface membrane was smooth whether the lungs were fully inflated or collapsed.


Acidosis and hypercalciuria: renal mechanisms affecting calcium, magnesium and sodium excretion in the sheep. 1. Observations were made on the excretion of calcium and magnesium by the sheep's kidney following manipulation of the acid-base status.2. Intravascular administration of a synthetic solution resembling saliva abolished the naturally occurring acidosis in sheep during feeding, and it also prevented the normal onset of post-prandial hypercalciuria and hypermagnesiuria.3. Non-respiratory acidosis (induced by infusion of hydrochloric acid) and respiratory acidosis arising from inhalation of 6% (v/v) CO(2) in air both caused an acute increase in calcium excretion.4. Measurement of filtered loads showed that feeding exerted an effect on the functional characteristics of the sheep's kidney. The renal clearances of calcium and magnesium increased, whereas sodium clearance decreased.5. Experimental conditions were arranged so that variations in acid-base status could be imposed at a time when the filtered load of calcium was declining.6. With hydrochloric acid-acidosis the renal excretion of calcium increased, despite a steady fall in the filtered load. With sodium bicarbonate alkalosis, the filtered load and the renal excretion of calcium decreased in unison.7. These variations in calcium excretion were not accompanied by corresponding changes in the excretion of sodium.8. It is concluded that the renal tubules in the sheep are sensitive to acid-base status and that they respond to a lowering of the blood pH by decreasing the tubular reabsorption of filtered calcium.


The contribution by glial cells to surface recordings from the optic nerve of an amphibian. 1. The contribution by glial cells to surface recordings has been examined in the optic nerve of the amphibian Necturus maculosus. The method of current injection was employed selectively to alter the membrane potential of glial cells without affecting that of the axons. The resulting changes in potential were recorded simultaneously from the surface of the nerve using the sucrose gap method and intracellularly from a glial cell near the gap.2. The sucrose gap method recorded 40% of the changes in glial membrane potential. This percentage was not affected when the current electrode was inserted into different glial cells while maintaining the recording conditions constant.3. Following axonal degeneration, produced by removing the eye 2-3 months earlier, the percentage contribution by glia increased to 84%.4. By measuring sucrose gap responses to changes in K(o) it was possible to estimate that the sucrose gap method recorded 31-60% of changes in axonal membrane potential. It was also determined that the axons, unlike glial cells, are relatively insensitive to reductions in K(o). Surface responses to decreases in external potassium thus reflect the magnitude of the glial contribution.5. It is concluded that changes in glial membrane potential contribute about as much to surface recordings from the optic nerve of Necturus as do equivalent changes in axonal membrane potential. The contributions by the glial cells and axons are related to the relative volumes of tissue they respectively occupy. The significance of these findings to the analysis of surface recordings from the mammalian brain is discussed. Since mammalian glial cells, like those in Amphibia and the leech, become depolarized during neuronal activity and on the basis of electron microscopic evidence appear to be electrically coupled, it is likely that they contribute to the electroencephalogram.


Development of the differential response to succinylcholine in the fast and slow-twitch skeletal muscle of the kitten. 1. The response to SCh has been studied in anterior tibialis and soleus muscles of new-born and neonate cat while, in a separate group of animals of similar ages, the end-plate development in these muscles has been examined.2. At birth, when the contraction times of the anterior tibialis and soleus are not statistically different, the anterior tibialis is 1.4 times more sensitive to SCh blocking action than the soleus, but both muscles were 20-40 times less sensitive than their adult counterparts.3. With maturation, the ratio of the soleus/anterior tibialis contraction time increased to 2.7 while the ratio of the 50% blocking dose of SCh in the soleus/anterior tibialis increased to 2.8, the increases being parallel. The time to 50% recovery at 50% blocking doses of SCh was similar for both muscles at all ages although it was 3 times longer in new-born and 1-week-old animals than in animals 3 weeks of age and older.4. The areas of individual end-plates from these muscles were very similar at birth but by three weeks of age the areas of end-plates from the anterior tibialis were substantially greater than those obtained from soleus.5. We have speculated that the relationship between SCh sensitivity and end-plate area in fast and slow muscle may find its origins in the frequency of the MEPP.


Observations on the mechanism of salicylate-induced antipyresis. 1. Fever has been produced in conscious rabbits, first, by injection of leucocyte pyrogen into the lateral cerebral ventricle and, second, by local cooling of the hypothalamus.2. Both intravenous and intraventricular salicylate produce antipyresis during an established fever due to intraventricular leucocyte pyrogen. This is incompatible with the hypothesis that salicylate acts by interfering with the passage of leucocyte pyrogen from the circulation into the hypothalamus.3. Intravenous sodium salicylate has no effect on the fever due to local cooling of the hypothalamus. This suggests that salicylates do not act on central or peripheral efferent pathways involved in thermoregulation.


The transparency of the mammalian cornea. 1. A theoretical and experimental analysis of the relationship of the corneal stromal ultrastructure with light transmission has been made in an attempt to resolve recent contradictory explanations of corneal transparency.2. The spatial distribution of collagen fibrils in electronmicrographs of rabbit corneal stroma has been analysed in terms of a radial distribution function. The results indicate the presence of local order extending to at least 200 nm from individual fibrils.3. The observed spatial distribution of the collagen fibrils was used as a basis to compare the theoretically derived and the experimentally determined values of light transmission. It has been found that the transparency of the normal cornea may be explained by the quasi-random structure revealed by the electronmicroscope.4. Histograms of the collagen fibril diameter in normal rabbit corneal stroma revealed the range to be 12.5-32.5 nm and the mean value to be approximately 20 +/- 1.5 nm. Corneal swelling did not change the collagen fibril diameter significantly.5. It is concluded that the size and distribution of collagen fibrils revealed in electronmicrographs are consistent with the observed transparency of normal stromas.6. A marked heterogeneity in the spatial distribution of collagen fibrils was found in the swollen cornea. This is qualitatively consistent with the observed decrease in transparency.


Autonomic effector responses to stimulation of nucleus fastigius. 1. In anaesthetized cats electrical stimulation of the nucleus fastigius caused cardiovascular responses, electrodermal responses of the paws and pupil dilation with retraction of the nictitating membranes.2. The cardiovascular responses included rise of arterial pressure and peripheral vasoconstriction. Increase of pulse pressure and tachycardia also occurred.3. The effects of sympathetic blocking drugs indicate that fastigial stimulation causes sympathetic discharge to the heart and to the peripheral vessels. There was no evidence of alteration of vagal activity.4. Fastigial stimulation inhibited reflex bradycardia due to carotid sinus distension, vagal afferent stimulation or phenyl diguanide.5. Fastigial and hypothalamic influences on cardiovascular responses could be evoked after severing the nervous pathways connecting the two.6. The pressor response to fastigial stimulation was still present after bilateral division of the carotid sinus and vagus nerves.


Spontaneous activity of neurones of nucleus reticularis thalami in freely moving cats. 1. Fifty-four neurones of the caudal part of the nucleus reticularis thalami (nuc. ret.) were recorded during different phases of sleep and wakefulness in unanaesthetized freely moving cats.2. During wakefulness the activity of the neurones was characterized by a continuous, well-spaced discharge. The mean firing rate was 35.58 +/- 15.06 spikes/sec (average +/- S.D.).3. During sleep with synchronized e.e.g. (S-sleep) the neurones fired in high frequency bursts with long pauses in between. Each burst was formed of 10-15 spikes. Often the bursts were followed by prolonged discharges formed of spikes well spaced one from the other. Bursts followed by prolonged activity were more commonly observed at the beginning of S-sleep and during the S-sleep periods preceding sleep with desynchronized e.e.g., whereas bursts immediately followed by silence were more frequent in the S-sleep periods with e.e.g. delta waves. The long periods of silence between the bursts usually lasted over 200 msec and values greater than 1 sec were frequently found. The mean firing rate of neurones during S-sleep was 19.22 +/- 10.50 spikes/sec.4. During sleep with desynchronized e.e.g. (D-sleep) the activity of the neurones was, as during wakefulness, characterized by a continuous, well spaced, unclustered discharge. The mean firing rate was 40.00 +/- 18.74 spikes/sec. During the rapid eye movements of this phase most units increased the frequency of their discharge, which, nevertheless, maintained the unclustered feature proper to the desynchronized phase of sleep.5. Interspike interval distribution was similar during wakefulness and sleep with desynchronized e.e.g., whereas that for sleep with synchronized e.e.g. was markedly different from those for both the other stages.6. The implications of the striking similarity between the activity of reticularis neurones during wakefulness and sleep with desynchronized e.e.g. are discussed.


Skeleto-fusimotor fibres in the rabbit.

Skeleto-fusimotor fibres in the rabbit. 1. In rabbits, repetitive stimulation of single motor axons to lumbrical muscles elicits both a contraction of extrafusal muscle fibres and an increase in the discharge frequency of spindle primary endings.2. This activation of the sensory endings can be attributed to the contraction of intrafusal muscle fibres because it persists after the contraction of extrafusal muscle fibres has been suppressed by selective curarization of their neuromuscular junctions.3. In non-curarized preparations the frequency of most of the afferent discharges continues to increase when rates of stimulation of motor fibres exceed the tetanic fusion frequency of the extrafusal muscle fibres.4. The effect of repetitive stimulation of motor fibres that supply extrafusal and intrafusal muscle fibres was studied on the responses of primary endings to phasic stretch. Of twelve fibres, eight were found to exert a dynamic effect and four a static one.5. Selective curarization of the extrafusal neuromuscular junctions does not modify the nature of the static and dynamic effects.


Modification of transmitter release by ions which prolong the presynaptic action potential. 1. The action of ions which increase the nerve spike duration at Ranvier's node has been studied at the neuromuscular junction of the frog.The duration of the presynaptic action potential is increased by UO(2), Ni, Nz and TEA ions.2. The release of transmitter after a nerve impulse is delayed and prolonged in the presence of the four ions, but the amount of evoked transmitter release estimated from the mean quantal content of e.p.p. is increased only by UO(2) (2+) and TEA. Both Ni(2+) and Zn(2+) decrease it.3. The frequency of m.e.p.p.s is increased by UO(2) (2+) and decreased by Ni(2+) and Zn(2+) at KCl-depolarized junctions. It is not affected by TEA.4. It has been concluded that the increased presynaptic spike duration is responsible for the delayed and prolonged transmitter release in the presence of ions which increase the nerve spike duration at Ranvier's node. It is demonstrated that some ;specific' effects possibly resulting from ionic competition for presynaptic sites between UO(2) (2+), Ni(2+) or Zn(2+) and other ions present in the Ringer may increase, interfere with, or hide the increased transmitter release that may be predicted from the lengthened presynaptic depolarization.


Direct and indirect activation of the hippocampus by tubocurarine. 1. In cats anaesthetized with intravenous chloralose, tubocurarine was either perfused through the inferior horn of a lateral ventricle or applied by micro-injection into the hippocampus, and the electrical activity was recorded from the surfaces of the occipital cortices and from the cannulae used for the perfusion or injection which, insulated except at their tips, served as recording electrodes as well.2. With both methods, the hippocampus became activated by tubocurarine acting directly on the hippocampus. The activation resulted in an abnormal spike discharge interrupted from time to time by short bursts of fast activity, termed episodes, followed by periods of electrical silence during which no abnormal activity was recorded. This abnormal discharge was recorded in all leads. The spikes were negative when recorded from the surface of the hippocampus, but changed polarity when the electrode was lowered and penetrated the pyramidal cell layer, and on further lowering the electrode the positive spikes increased in voltage up to 15 mV and then decreased.3. With both methods, signs of indirect activation of the hippocampus were observed when the tubocurarine set up foci of excitation in one of the following three areas of cerebral cortex which lie ventral to the hippocampus, the Area entorhinica, the Area perirhinica and the Area post-splenialis. The foci of excitation resulted in a continuous discharge of negative spikes which were recorded in the leads from these areas only. A characteristic feature of the indirect hippocampal activation arising from the continuous discharge set up in the Area post-splenialis was the periodicity. Activation lasting 20-60 sec occurred every few minutes or at shorter intervals, often leading to an episode.


Factors controlling the secretion of a substance biologically resembling the 18-monoacetate of D-aldosterone by heart muscle. 1. Previous work has demonstrated that the cat heart secretes a substance which resembles the 18-monoacetate of D-aldosterone (18 MA) in chromatographic properties and biological actions. This substance (HS) releases ADH from the neurohypophysis and, in higher concentration, causes renal retention of salt and water. HS is extracted from blood, separated chromatographically and assayed in terms of equivalent 18 MA activity either by inhibition of water diuresis in rats or by reduction of the excretion of Na by the isolated kidney. Positive correlation has been demonstrated between heart rate and HS secretion.2. Heart-lung preparations from cats have been used to disclose additional factors controlling the rate of secretion of HS from heart muscle.3. Positive inotropic effects produced by administration of digoxin or adrenaline or by increase in peripheral resistance are associated with increases in the secretion of HS.4. Negative inotropic effects produced by high concentrations of procaine hydrochloride or by increase in venous return without change in external work are associated with decrease in HS secretion.


The perceived spatial frequency shift: evidence for frequency-selective neurones in the human brain. 1. Prolonged observation of a high-contrast grating pattern causes an apparent shift in the spatial frequency of gratings subsequently viewed with the same retinal region. Gratings of higher and lower frequency than the adapting pattern seem, respectively, higher and lower than in fact they are.2. There is no significant after-effect at the adapting frequency itself nor at frequencies more than two octaves away.3. For very low adapting frequencies, the after-effect remains centred at about 3.0 c/deg and declines in strength as the adapting frequency is successively lowered.4. The magnitude of the after-effect increases with the contrast of the adapting grating and the length of time spent in adaptation. It takes several hours to recover completely from 30 min adaptation.5. The phenomenon is orientation-specific: a horizontal adapting grating has no effect on vertical test gratings. There is partial interocular transfer of the after-effect.6. These findings provide further evidence that the visual system of man, like those of the cat and the monkey, contains neurones selectively sensitive to the orientation and dimensions of retinal images, and that these adaptable cells are actually involved in the encoding and perception of the size of simple patterns.


Centrifugal inhibitory processes affecting neurones in the cat cochlear nucleus. 1. Stimulation of the lateral part of the olivary S-segment in the cat inhibited neurones in the ipsilateral cochlear nucleus. A smaller number of neurones located in the ventral division of the cochlear nucleus were excited.2. It is suggested that inhibition in the ipsilateral cochlear nucleus may be mediated directly by fibres making synaptic connexions on the cochlear nucleus neurones, or indirectly by inhibitory fibres acting at the cochlea.3. The direct inhibitory process at the cochlear nucleus is unaffected by strychnine, whereas the inhibitory process at the cochlea is abolished by strychnine.4. A cochlear nucleus neurone can be influenced simultaneously by excitatory and inhibitory processes.


Effects of changes of ionic environment on the negative after-potential of the spike in rat uterine muscle. 1. The spontaneous activity of the smooth muscle of rat uterus consists of bursts of spikes, each spike being followed by a negative after-potential. The effect of changes in ionic environment on the negative after-potential was investigated at various stages of pregnancy and in the non-pregnant condition.2. The amplitude of the negative after-potential was the same in spontaneously generated and electrically evoked spikes. During repetitive discharge, whether spontaneous or in response to depolarizing current application, the amplitude of the after-potential was smallest in the first spike of a burst and it increased gradually with repetition of discharge.3. The decay of the negative after-potential was slower than the passive return of the membrane potential to its resting level.4. The amplitude of the negative after-potential was larger in non-pregnant uterus than during late pregnancy.5. In pregnant uterus, the replacement of the Cl in the medium with benzene sulphonate transiently augmented the negative after-potential and then gradually reduced it. Eventually, the negative after-potential disappeared and, instead, a positive after-potential was observed. This conversion took place without a noticeable change in the resting potential or in the initial falling phase of the action potential itself. Replacement of Cl with NO(3) had no appreciable effect on the negative after-potential.6. In non-pregnant uterus, the conversion of the negative to a positive after-potential was never observed. However, in Cl-deficient solution the size and duration of the negative after-potential were reduced.7. In Cl-deficient solution (benzene sulphonate substitution), the decay of the electrotonic potential following the break of cathodal current became faster than that in normal solution. On the other hand the development of the anodic electrotonic potential became slower.8. Replacement of the NaCl in the medium with sucrose converted the negative after-potential to a positive after-potential. On the other hand, reduction of Na only by replacement of NaCl with Tris-Cl had no noticeable effect on the negative after-potential.9. It is concluded that the negative after-potential of the spike in rat uterine muscle is largely due to an increase of Cl conductance of the membrane.


Non-cholinergic transmission by post-ganglionic motor neurones in the mammalian bladder. 1. In mucosa-free preparations of the detrusor muscle electrical stimulation with 0.1 msec pulses has been utilized to reveal the non-cholinergic nature of most, if not all, of the post-ganglionic motor neurones in the guinea-pig bladder.2. The twitches elicited by 0.1 msec pulses were abolished by tetrodotoxin, but were not reduced by dimethyltubocurarine or by hexamethonium. Hexamethonium was nevertheless present in all the experiments in order to restrict acetylcholine action to ;muscarinic' receptors in the muscle fibres.3. There was little or no diminution in the twitches after prolonged exposure to atropine, 10(-8)-10(-5) g/ml., although the twitch-matching dose of acetylcholine was raised 1000-2500 times. Hence, there was no anomalous refractoriness to atropine in these ;muscarinic' receptors.4. Despite massive atropinization, the recruitment of unoccupied transmitter-receptors by means of extra pulses remained unaffected.5. Eserine failed to potentiate the atropine-resistant twitches.6. The twitches were not depressed by morphine.7. Noradrenaline produced relaxation and twitch reduction. The twitches persisted after alpha + beta adrenoceptor blockade with phentolamine + pronethalol and were unaffected by the monoamine oxidase and catecholamine-O-methyl transferase inhibitors, tranylcypromine and pyrogallol.8. Rapid contractions were elicited by 5-HT and by histamine but the twitches remained unaltered after antagonism of 5-HT by methysergide and of histamine by mepyramine.9. The twitches could be mimicked by injections of ATP, but after desensitization of the preparation to ATP the response to electrical stimulation remained unaltered.10. Prostaglandins E(2) and F(2alpha), only in large doses, produced delayed, sluggish contractions which persisted after the wash; these contractions were quite different from the responses to electrical stimulation, which were immediate, sharp and brief.11. The non-cholinergic nature of the post-ganglionic motor neurones was confirmed in the bladder of two other species, the cat and the rabbit.


The possible role of microbial L-forms in pyelonephritis.


The scintillation camera in embolic acute renal failure.


Transvesical ureterectomy.

Transvesical ureterectomy.


Favorable experience with silicone circle ureterostomy tube diversion.


Electronic lithotripsy: transurethral treatment of bladder stones in 50 cases.


Testicular biopsy findings in patients with impaired fertility.


The role of lymphoid reaction in bladder cancer.


Autogenous perineal bone graft for post-prostatectomy incontinence. II. Technique and results of prosthetic fixation of urogenital diaphragm in man.


Late results following cryosurgery of the prostate (a clinical and panendoscopic study of 80 patients).


Urine collection problems in the space program.


Atabrine as an adjuvant in chemotherapy of urinary tract infections.


Transmission of M. tuberculosis via genital tract.


Electronic instrument for supervising catheters and probes.


More than knowing. Clergymen: their attitudes toward and knowledge of the mentally retarded.


In defense of intelligent behavior.

In defense of intelligent behavior.


Meeting the challenge of dental care for retarded and physically handicapped children.


Preparation of thin dust coatings for their analysis by x-ray emission and di- ffraction.


Hazards from products of combustion and oxygen depletion in occupied spaces.


Direct x-ray diffraction quantitative analysis of quartz in industrial dust films deposited on silver membrane filters.


Note on the personality traits of student nurses.


Acceptance of generalized versus "bona fide" personality interpretation.


Sexual differences in physical attractiveness as a determinant of heterosexual liking.


Secondary reinforcement based on primary brain stimulation reward.


Relation between attempted suicide and completed suicide.


Brief note on the reliability of the Janis and Field "Feelings of Inadequacy" scale.


Persistence of ethnic stereotypes and the relative importance of positive and negative stereotyping for association preferences.


Student acceptance of bogus personality interpretations differing in level of social desirability.


Is hunger drive held constant in the behavior experiment employing a fixed food-deprivation schedule?


Relationship between somatization and effects of stress on electrogastric waveforms in humans.


Suicidal behavior and external constraints.


The breakdown of the American image: comparison of stereotypes held by college students over four decades.


Hypnosis and the desensitization behavior therapies.


Personality Adjective List. I. Factor structure for a combined sample of male and female college students.


Completed suicide and latitude.

Completed suicide and latitude.


An unobtrusive measure of prejudice toward Negroes under differing durations of speech.


Item-analysis procedures for enhancing validity of existing personality scales.


A view of Levonian's remarks on studies of self-esteem and persuasibility.


A scale of Black separatism.

A scale of Black separatism.


Note on level of aspiration as a selective device for psychiatric aides.


Altruism in college women.

Altruism in college women.


The Mini-Mult as a personnel screening technique: a preliminary report.


Mass function and equipotentiality: a reanalysis of Lashley's retention data.


Effect of REM sleep deprivation on exploration in rats.


Death as a psychosomatic condition: prolegomena to a longitudinal study.


Relationships between hostility guilt and several measures of hostility.


Measuring racial attitudes in a situational context.


Dubin-Johnson syndrome in Israel. II. Association with factor-VII deficiency.


Glomerular coagulation in acute ischaemic renal failure.


One approach in rehabilitating the retarded.


Rehabilitation environment 1970.

Rehabilitation environment 1970.


The structure of aquayamycin.

The structure of aquayamycin.


The isolation and structure of two new indole derivatives from Penicillium cyclopium westling.


Antituberculosis agents. I. Alpha-(5-(2-Furyl)-1,2,4-triazol-3-ylthio) acethydrazide and related compounds.


Optical rotatory properties of methylisothiocyanate-amino acid adducts.


Synthesis and conformational study of some diastereoisomeric 4-methyl-3-phenyl-3-piperidinols and related esters.


Etiologic diagnosis of retinal venous stasis and occlusion.


Modified forehead flap repair in oropharyngeal carcinoma.


Vitrectomy in cataract and corneal surgery.


Filtering conjunctival blebs as a complication of cataract extraction.


Cataract complicated by glaucoma or by corneal disease.


Partial laryngectomy.

Partial laryngectomy.


Surgical treatment of jaw-winking ptosis.


Management of retinal venous stasis and occlusion.


Treatment of cancer of the anterior floor of the mouth.


Surgery of the parotid gland.

Surgery of the parotid gland.


Treatment of retinal vascular disease with argon laser slit lamp photocoagulation.


Frontal bone conduction, impedance, and myringomanometry in the diagnosis of conductive lesions.


Results of tympanic neurectomy for Frey's syndrome.


Tuning forks in modern otology.

Tuning forks in modern otology.


IUPAC-IUB Commission on Biochemical Nomenclature (CBN). Abbreviations and symbols for nucleic acids, polynucleotides and their constituents. Recommendations 1970.


Specificity and locale of the L-3-glycerophosphate-flavoprotein oxidoreductase of mitochondria isolated from the flight muscle of Sarcophaga barbata thoms. 1. The oxidation of l-3-glycerophosphate by flight-muscle mitochondria isolated from the flesh fly Sarcophaga barbata has been studied. Use of substrate analogues indicates that the catalytic and effector l-3-glycerophosphate binding sites on the allosteric l-3-glycerophosphate-flavoprotein oxidoreductase differ markedly in specificity. 2. The l-3-glycerophosphate-cyanoferrate oxidoreductase system in these mitochondria is antimycin-insensitive whereas the corresponding NADH-cyanoferrate oxidoreductase is extremely sensitive to this respiratory-chain inhibitor. Also no swelling is observed when these mitochondria are suspended in iso-osmotic solutions of ammonium glycerophosphate in contrast with the extensive swelling seen in similar solutions of ammonium pyruvate. These observations indicate that l-3-glycerophosphate does not penetrate the mitochondrial matrix whereas pyruvate does. 3. Submitochondrial particles catalyse the ATP-driven reduction of NAD(+) by l-3-glycerophosphate but at a far lower rate than that seen when succinate is the electron donor. These particles do not have an energy-linked pyridine nucleotide transhydrogenase activity. 4. We conclude that the l-3-glycerophosphate-flavoprotein oxidoreductase is located on the outer surface of the inner membrane of the flight-muscle mitochondria.