bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐synaptic potentiation: interaction between quanta of acetylcholine at the skeletal neuromuscular synapse.
Authors: Hartzell H C , Kuffler S W , Yoshikami D
Published: December 2014

1. Post‐synaptic responses to acetylcholine (ACh) released from nerve terminals and from iontophoretic micropipettes were investigated in skeletal muscle fibres of the snake. Each fibre has a compact end‐plate consisting of fifty to seventy synaptic boutons. The fibres were voltage clamped, and synaptic currents were recorded from visually identified end‐plates. 2. When acetylcholinesterase (AChE) is inhibited, a potentiating interaction is observed between two or more quanta that are released close to each other from a synaptic bouton and act upon partially overlapping postsynaptic areas. The potentiation is expressed as a prolongation of the synaptic current. This potentiation also occurs under normal conditions of release when about 300 quanta are distributed over the entire end‐plate, so thet the presynaptic release sites are separated by an average of 2 mum. An analogous potentiating interaction is observed when micropipettes, closely apposed to the subsynaptic membrane, substitute for quantal release sites. ACh from one pipette potentiates the response to ACh from another pipette less than 2 mum away. 3. In contrast, with AChE fully active no post‐synaptic potentiation is seen when the normal complement of quanta is released over the entire end‐plate. The time course of the synaptic currents in response to a single quantum or to 300 quanta is similar. It is concluded that functionally the quanta act independently of each other, because AChE isolates each quantum from its neighbours by limiting the lifetime of ACh and its lateral diffusion in the synaptic cleft. The estimated area over which a quantum normally acts is less than 2mum2. 4. Post‐synaptic receptors are not saturated by the ACh in a quantum, since the peak of the quantal response adds linearly to the response produced by an appropriate background concentration of ACh from a pipette. This conclusion is supported by the observation that upon inhibition of AChE the peak amplitude of the quantal current response increases by about 20% with no change in its time to peak. 5. It is suggested that post‐synaptic potentiation between quanta may play a role in signalling at synapses in which non‐linear dose‐response characteristics have been observed and where transmitter is not as repidly inactivated as the neuromuscular synapse.
Cortical and long spinal actions on lumbosacral motoneurones in the cat.
Authors: Aoki M , McIntyre A K
Published: December 2014

1. The effects of stimulating forelimb afferents on various ipsilateral motoneurones of the hind limb have been compared with those of volleys set up in the contralateral pericruciate cortex in cats anaesthetized with chloralose. 2. With intact neuraxis, brachial plexus volleys evoke discharge of flexor and extensor motoneurones; short cortical tetani also elicit discharge mainly of flexor motoneurons. After a pyramid‐sparing brainstem lesion, little or no firing is evoked by either input. 3. Monosynaptic reflex testing and intracellular recording reveal subthreshold actions on hind‐limb motoneurones, inhibition of FDHL and later facilitation of extensors and flexors by forelimb volleys, facilitation of flexors and extensors together with inconstant inhibition of the latter, by cortical stimulation. 4. Interruption of medullary extrapyramidal paths greatly reduces intensity and duration of facilitation from the forelimb, and largely removes cortically evoked extensor facilitation. Inhibition of FDHL from forelimb and cortex is unchanged; cortical volleys continue to facilitate flexors, and have mainly inhibitory action on extensors in these 'pyramidal' preparations. 5. Hyperpolarization of FDHL motoneurones occurs in response to forelimb and cortical volleys, of time course corresponding to depression of test reflexes. Spinal pathways responsible for the two inhibitory actions are independent, and unless each is very strong, their separate actions summate when elicited together. 6. Receptive field for FDHL inhibition from the forelimb is located distally in the forepaw, and its receptors are largely served by cutaneous fibres of low threshold; some Group II fibres in distal muscle nerves also contribute. Receptive field for facilitation embraces the whole limb, and the executant afferent fibres are of higher threshold. 7. Natural stimulation of the forelimb can evoke the long spinal actions, vibration or light pressure on the forepaw eliciting FDHL inhibition, and strong pinching evoking the more general facilitation. Possible functional roles of these actions in the intact animal are discussed.
Transfer of fatty acids across the rabbit placenta.
Authors: Elphick M C , Hudson D G , Hull D
Published: December 2014

1. Transfer of fatty acids across the placenta was studied in anaesthetized rabbits at 28‐days gestation by measuring umbilical venous‐arterial differences, by injection of labelled palmitate into the mother and observing its appearance in the foetus, by injection of labelled palmitate into the foetus and measuring its appearance in the mother and the foetal clearance rate. 2. The release of fatty acids and glycerol by foetal adipose tissues was investigated in vitro by measuring the effect of addition of noradrenaline to the incubation medium and in vivo by measuring the effect of noradrenaline infusion into the foetus on circulating glycerol and free fatty acid concentrations. 3. In anaesthetized rabbits at 28‐days gestation the maternal circulating free fatty acid concentrations were high and there was a positive umbilical venous‐arterial difference. High maternal free fatty acid concentrations were associated with high umbilical venous‐arterial differences. 4. Label was present in the foetus in 2 min and reached a peak in 3 min after injection of labelled palmitate into the mother. Label appeared in the maternal circulation in 1 min after injection into the foetus. The half‐life of labelled palmitate was of the order of 30‐60 sec in both mother in foetus. 5. Foetal white adipose tissue released both free fatty acids and glycerol into the medium and the rate of release increased four to five fold after addition of noradrenaline. Infusion of noradrenaline in the foetus led to a rise in glucose and glycerol concentrations, but the change in free fatty acid concentrations was not significant. 6. It was concluded that (i) free fatty acids can cross the rabbit placenta in amounts sufficient to provide the fatty acid components of stored triglyceride and structural lipids; (ii) placental transport of free fatty acids depends in part on maternal blood concentration and on foetal uptake; (iii) foetal circulating free fatty acids are continually exchanging with fatty acid pools in the placenta and with the maternal circulating free fatty acids.
Effect of insulin upon membrane‐bound (Na+ + K+)‐ATPase extracted from frog skeletal muscle.
Authors: Gavryck W A , Moore R D , Thompson R C
Published: December 2014

1. Insulin stimulates the activity of membrane‐bound ATPase isolated from frog skeletal muscle and from rat brain. The increase in activity of the membrane‐bound ATPase system isolated from frog ranged from 9‐8 to 53% at concentrations of Na+ (25 mM), K+ (10 mM), and ATP (2 mM) similar to those in in vivo experiments conducted previously (Moore, 1973). The increased activity of the membrane‐bound ATPase is, therefore, at least as great as the insulin‐induced increase in Na efflux (10‐38%) from intact cells (Moore, 1973). If the concentration of Na+ is lowered to 4 mM and that of ATP lowered to 0‐5 mM albumin, and 10(6) M, the increase in ouabain‐inhibitable ATPase activity can reach as high as 400%. 2. Ouabain, at a concentration (10(‐3) M) sufficient to inhibit stimulation of the frog ATPase by increasing Na from 4 to 25 mM, completely blocked the stimulation of ATPase activity due to insulin. 3. At 2 mM‐ATP, 100 mM‐Na+, and 20 mM‐K+, conditions which maximally activate the (Na+ + K+)‐ATPase, insulin did not increase the ATPase, activity. Stimulation was consistently seen at 10 mM‐K+, 0‐5 mM‐ATP, and either 4 mM or 25 mM‐Na+. 4. The finding that insulin does not stimulate the ATPase activity in conditions in which the (Na+ + K+)‐ATPase component is maximally activated and especially the fact that ouabain can reproducibly inhibit insulin stimulation of the membrane‐bound ATPase activity strongly suggest that interaction of insulin with its receptor upon the plasma membrane somehow stimulates the (Na+ + K+)‐ATPase system (ouabain sensitive; ATP phosphohydrolase, EC (3.6.1.3). These results are consistent with previous studies of the effect of insulin upon Na efflux from intact cells (Moore, 1973) and support the previous conclusion that the component of Na efflux stimulated by insulin is active. The evidence suggests that insulin probably does not affect Vmax of the (Na+ + K+)‐ATPase system, but may increase the affinity of the enzyme system to one or more effectors, most likely Na+, ATP, and perhaps K+. 5. Oxidized glutathione (2‐7 X 10(‐6) M), 10(‐6) M, 10(‐7) M, and 10(‐8) M cyclic AMP did not affect the ATPase activity 10(‐6)Malbumin, and . 6. The results are consistent with the view that the Na pump, (Na+ + K+)‐ATPase, is intimately involved with the physiological action of insulin and may be transducer between the binding of insulin to its receptor on the plasma membrane and the cellular actions of insulin.
The influence of pH on equilibrium effects of tetrodotoxin on myelinated nerve fibres of Rana esculenta.
Authors: Ulbricht W , Wagner H H
Published: December 2014

1. The experiments were done on single nodes of Ranvier of Rana esculenta. The effects of tetrodotoxin and H ions were determined either by the reduction of the maximum rate of rise, VA, of action potentials evoked with threshold stimuli or in the voltage clamp by the decrease of the peak Na permeability, PNa. 2. With the tetrodotoxin sample used throughout the investigation the equilibrium dissociation constant, KT, of the toxin‐receptor reaction at neutral pH was determined to be 2‐8 nM. Between 1‐55 and 15‐5 nM tetrodotoxin the normalized value, A, of VA, was found to be related to the normalized toxin concentration cT = [TTX]/2‐8 nM by the empirical equation log [(1‐A)/A] = 1‐22 log cT‐0‐573. 3. On increasing the pH (up to 8‐8) the effect of tetrodotoxin diminished as revealed by an increase in A. The apparent reduction of cT (as calculated from A) suggests that the toxin is active only in its cationic forms. 4. Weakly acid tetrodotoxin solutions (7‐3 less than pH less than or equal to 5‐5) reduced A to a lesser degree than did neutral toxin solutions in spite of the inherent depressing effect of acid pH on A (A = 0‐5 at about pH 5‐5). In more acid toxin solutions A decreased again and at pH 4‐6 it was about equal to the value in toxin‐free solution. 5. When, after equilibrium in an acid toxin solution, the perfusate was suddenly changed to neutral Ringer solution A jumped to a higher value A' as measured 1 sec after the switch. Since the blocking effect of hydrogen ions subsided within a fraction of a second while the time constant of the toxin washout is of the order of 1 min, A' reflects the number of Na channels blocked by tetrodotoxin at acid pH. 6. In acid toxin‐free solution the peak PNa as obtained in voltage clamp experiments was reduced by a voltage‐dependent factor (cH + 1)‐1 with CH = [H+]/KH(E) and KH(E) = 2‐04 muM exp (0‐34 EF/RT). Adding tetrodotoxin resulted in another reduction by a constant factor p'T. 7. Experiments employing various combinations of toxin concentration (3‐1‐93 nM) and pH values (7‐3‐5‐2) confirm the decreased toxin effect at low pH. Moreover, p'T was smaller (the additional toxin effect larger) when the membrane had been kept depolarized and thus cH reduced during equilibration. This suggests that tetrodotoxin cations and H ions compete for the same blocking site. A quantitative fit, however, requires additional assumptions.
Mechanical properties of frog skeletal muscles in iodoacetic acid rigor.
Authors: Mulvany M J
Published: December 2014

1. Methods have been developed for describing the length: tension characteristics of frog skeletal muscles which go into rigor at 4 degrees C following iodoacetic acid poisoning either in the presence of Ca2+ (Ca‐rigor) or its absence (Ca‐free‐rigor). 2. Such rigor muscles showed less resistance to slow stretch (slow rigor resistance) that to fast stretch (fast rigor resistance). The slow and fast rigor resistances of Ca‐free‐rigor muscles were much lower than those of Ca‐rigor muscles. 3. The slow rigor resistance of Ca‐rigor muscles was proportional to the amount of overlap between the contractile filaments present when the muscles were put into rigor. 4. Withdrawing Ca2+ from Ca‐rigor muscles (induced‐Ca‐free rigor) reduced their slow and fast rigor resistances. Readdition of Ca2+ (but not Mg2+, Mn2+ or Sr2+) reversed the effect. 5. The slow and fast rigor resistances of Ca‐rigor muscles (but not of Ca‐free‐rigor muscles) decreased with time. 6.The sarcomere structure of Ca‐rigor and induced‐Ca‐free rigor muscles stretched by 0.2lo was destroyed in proportion to the amount of stretch, but the lengths of the remaining intact sarcomeres were essentially unchanged. This suggests that there had been a successive yielding of the weakeast sarcomeres. 7. The difference between the slow and fast rigor resistance and the effect of calcium on these resistances are discussed in relation to possible variations in the strength of crossbridges between the thick and thin filaments.
Cinematographic analysis of contractile events produced in intrafusal muscle fibres by stimulation of static and dynamic fusimotor axons.
Authors: Bessou P , Pagés B
Published: December 2014

1. Muscle spindles with an intact blood supply and uninterrupted connexions with ventral and dorsal spinal roots (Bessou & Pagés, 1967, 1972) have been prepared in cat's tenuissimus muscles with the aim of cinephotographically recording intrafusal movements induced by the stimulation of single static or dynamic gamma axons; the time cours of these movements and the morphological kind of activated intrafusal muscle fibres have been established. 2. Displacements of spindle guiding marks in the equatorial region elicited by stimulating single static gamma axons are 4‐20 times greater in amplitude than the ones elicited by stimulating dynamic gamma axons at the same frequency. 3. The dynamic gamma axons induced a contraction only in nuclear bag fibres which, in addition, never received any static gamma innervation. The static gamma axons evoked contractions either in nuclear bag fibres alone, or in nuclear chain fibres alone, or in both types of intrafusal fibres. Two thirds of static gamma axons supplied nuclear bag fibres. For various reasons, one half only of static gamma axons innervating nuclear bag fibres could be shown to simultaneously innervate nuclear chain fibres. Consequently, about one third of static gamma axons supplied both nuclear bag fibres and nuclear chain fibres, but it is highly probable that this latter figure is an underestimate. One third of static gamma axons produced contraction in nuclear chain fibres only. In this work, the distribution of fusimotor axons has been established in only one muscle spindle of the cluster of muscle spindles that each fusimotor axon is generally innervating. 4. Generally speaking, a static gamma axon elicits contraction of several intrafusal fibres whereas a dynamic gamma axon innervates only one intrafusal fibre and frequently only one pole of the fibre. 5. One third of static gamma axons evoked contractions in nuclear chain fibres that seemed to involve the whole pole. The other static gamma axons and all dynamic gamma axons produced, in the intrafusal fibres that they supplied, one or several foci of localized contractions. 6. The nuclear chain fibres contract and relax faster than nuclear bag fibres. The contractions of nuclear bag fibres supplied by static gamma axons are stronger and faster than those of nuclear bag fibres innervated by dynamic gamma axons. Nearly all nuclear bag fibres innervated by static gamma axons, like the nuclear chain fibres, show transient contractions at each pulse of a stimulation at low frequency (2‐20/sec). 7. The results are discussed taking into account the available anatomical and physiological data on the muscle spindle. Their consequences with regard to intrafusal working are briefly considered.
Dissociation between nerve‐muscle transmission and nerve trophic effects on rat diaphragm using type D botulinum toxin.
Authors: Bray J J , Harris A J
Published: December 2014

Small doses of botulinum toxin can produce partial blockage of transmitter release at the nerve‐‐muscle junction. 2. Subthreshold e.p.p.s, 3‐‐10 days after poisoning, show a distribution of amplitudes that is fitted by Poisson statistics. Successive e.p.p.s. in a short train show a marked facilitation. 3. Two weeks or more after poisoning with a dose of toxin that paralyses the whole muscle, when nerve‐‐muscle transmission is in course of recovery, subthreshold e.p.p.s have an amplitude distribution that is fitted by binomial statistics. This property of transmission is similar to those described in newly formed nerve‐‐muscle junctions, during embryogenesis or regeneration. 4. Muscle fibres with subthreshold transmission in the 5‐‐10 day group of muscles were all supersensitive to ACh, as were a number of fibres in which nerve stimulation still produced an action potential. 5. Two weeks or more after poisoning, muscle fibres with subthreshold transmission had lost their extrajunctional ACh‐sensitivity, as had many fibres with m.e.p.p.s of roughly normal frequency but no response to nerve stimulation. 6. In diaphragm muscles poisoned with botulinum toxin between 1 and 4 days previously, the rate of fast axonal transport of radioactively labelled proteins down the phrenic nerve is not greatly affected, but the amount of materials carried is reduced to about one quarter of normal. These labelled proteins accumulate in the intramuscular portion of the phrenic nerve, in or near the nerve terminals, to a much greater extent than in controls, showing that the normal release of some of these materials has been prevented by the toxin. 7. It is concluded that the blockage of the trophic effects of nerves by botulinum toxin is due to a blockage of release of trophic factors other than ACh. 8. The muscle nerve cannot maintain a muscle in its normal state simply by activation of contraction, and a regenerating nerve terminal can restore a muscle towards its normal state before it can release enough ACh to produce muscle contraction.
Two phases of chorda‐lingual induced vasodilatation in the cat's submandibular gland during prolonged perfusion with Locke solution.
Authors: Poulsen J H
Published: December 2014

The effect of stimulation of the chorda‐lingual nerve on the venous flow has been studied in cat submandibular glands perfused with Locke solution for 2‐4 hr. When trains of pulses at 25 Hz were given for 1‐5 sec, two distinct phases of vasodilatation were observed: a rapid initial phase of high amplitude and a slower developing more prolonged phase of smaller amplitude. Repeated stimulations did not lead to a reduction of the vasodilatory response. A close relationship was found between the duration and magnitude of the second phase of vasodilatation and the duration and magnitude of the post‐stimulatory, active reuptake of potassium. When the active reuptake of potassium was prevented either by ouabain (which inhibits active transport) or by atropine (which abolishes the stimulation induced loss of potassium) the second phase of vasodilatation was severely reduced, while the initial phase remained virtually normal. It is concluded that the initial phase of vasodilatation probably is mediated by vasodilator nerve fibres. The second phase is perhaps causally related to the post‐stimulatory, active transport of cations. An involvement of bradykinin formation is highly unlikely under the given experimental conditions.
The effects of muscle cooling and stretch on muscle spindle secondary endings in the cat.
Authors: Michalski W J , Séguin J J
Published: December 2014

1. The objectives of the investigation were to identify the muscle spindle endings which respond to cooling of the relaxed muscle and to study their response to stretch. 2. The discharge of single afferents from 162 de‐efferented muscle spindles in the relaxed medial gastrocnemius muscle of the anaesthetized cat was studied in vivo during cooling of the muscle from 37 to 24 degrees C. Temperature measurements were made at the inner surface of the muscle, while cooling (never below 15 degrees C) was applied at the skin over the muscle. 3. The endings were classified as primary or secondary endings on the basis of their conduction velocity, the dividing line being set at 70 m/sec. A response to cooling was obtained only from endings with afferents conducting at velocities of 20‐70 m/sec. These fifty‐six endings (CR) represented 65% of the secondary endings studied; the remaining secondary endings (NCR) and the primary endings showed no activity during cooling of the relaxed muscle. 4. During maintained stretches of 4‐12 mm, activity of the NCR and primary endings decreased when the muscle was cooled. Cooling affected the CR endings in the same way, but only if the muscle was stretched 6 mm or more. During a smaller maintained muscle stretch, cooling caused an increase in CR activity, superimposed on the response to stretch. 5. The response to a 10 mm stretch at velocities of 10‐70 mm/sec was studied in twenty‐six CR, eleven NCR and twenty‐one primary endings. 6. The dynamic responses of CR endings were intermediate between those of the primary endings and NCR endings. For any velocity of stretch the mean dynamic index of the CR endings was significantly greater than that of the NCR endings but significantly less than that of the primary endings. 7. The mean static responses of the CR and primary endings, measured 0‐5 sec after the end of ramp stretch, were the same and significantly greater than that of the NCR endings. 8. The results indicate that cooling of the relaxed mammalian muscle may be used to differentiate between primary endings and about two‐thirds of the secondary endings. The remaining secondary endings can be recognized by their small dynamic and static response to stretch.
The effects of lanthanum and thulium on the mechanical responses of rat vas deferens.
Authors: Swamy V C , Triggle C R , Triggle D J
Published: December 2014

1. The contractile responses of rat vas deferens to noradrenaline and K+ are composed of phasic and tonic components both of which are dependent upon the concentration of extracellular Ca2+. 2. Lanthanum, La3+, and thulium ions, Tm3+, inhibited the noradrenaline and K+ induced responses, complete inhibition being obtained at approximately 10(‐3) M‐Ln3+. 3. La3+ and Tm3+ were equally effective in inhibiting noradrenaline and K+ responses. The phasic and tonic components of the noradrenaline response were equally sensitive to lanthanide cations, Ln3+, but the phasic component of the K+ response was more sensitive than the tonic component. 4. 170Tm binding did not show any saturable component over the concentration range in which inhibition of the pharmacological response was obtained. 5. It is suggested that the actions of Ln3+ in the rat vas deferens are mediated through some kind of membrane stabilization rather than via a specific Ca2+ binding site concerned with excitation‐contraction coupling, the mechanism previously postulated for the Ln3+ action in guinea‐pig ileal longitudinal muscle.
Functional and non‐functional contacts between ciliary neurones and muscle grown in vitro.
Authors: Betz W
Published: December 2014

1. In cultures of chick embryo skeletal muscle and ciliary ganglia, muscle fibres near a ganglion were contacted by many individual nerve processes. Experiments were performed to determine if these muscle fibres were multiply innervated, and if any of the nerve‐muscle contacts were non‐synaptic. 2. Synaptic potentials evoked by electrical stimulation of a ganglion were graded with stimulus strength. When two ganglia were plated near each other, synaptic potentials could be evoked in some muscle fibres by stimulation of either ganglion. These observations suggest that muscle fibres were multiply innervated. 3. Spontaneous synaptic potentials recorded from single muscle fibres with two widely spaced micropipettes varied in a manner which suggested that the synapses were distributed at different points on the surface of the muscle fibres. 4. Stimulation of some nerve processes failed to evoke synaptic potentials in muscle fibres contacted by those processes. Such nerve‐muscle contacts were not strongly adhesive, and the nerves were peeled easily from the surface of the muscle with a micropipette. On the other hand, nerve processes which formed synaptic contacts with muscle fibres seemed to be tightly adherent to the muscle. 5. Electron microscopic observations of nerve‐muscle contacts revealed that the vast majority of such contacts lacked morphological specializations characteristic of mature neuromuscular synapses.
Effects of isopropylnoradrenaline on tachyphylaxis of gastrin stimulated gastric acid secretion and mucosal blood flow in the anaesthetized cat.
Authors: Reed J D , Smy J R
Published: December 2014

1. Gastric acid and mucosal blood flow responses to sustained gastrin stimulation were studied in anaesthetized cats. 2. Acid and mucosal blood flow showed identical rates of tachyphylaxis to both large (maximal) and small doses of gastrin. 3. Isopropylnoradrenaline infused either intravenously or close arterially to the stomach produced increases in blood flow unrelated to time following the peak response to large doses of gastrin, whereas increases in acid secretion appeared to be a part removal of the acid tachyphylaxis. 4. During stimulation by small doses of gastrin, isopropylnoradrenaline increased both blood flow and acid secretion above the peak responses to gastrin alone. 5. Increases in gastrin stimulated acid and mucosal blood flow were also produced by expansion of the blood volume by dextran‐saline infusions. 6. The physiological significance of these findings is discussed. 7. It is concluded that tachyphylaxis of gastric acid secretion to gastrin may be a function of the primary tachyphylaxis of mucosal blood flow.
Increase by visual stimuli in turnover of 5‐hydroxytryptamine in the superior colliculi of the rabbit.
Authors: Fukui K , Vogt M
Published: December 2014

1. Irregular light falshes were played on to one eye of dark adapted rabbits for periods of 20‐80 min. The concentration of 5‐hydroxyindol‐3‐ylacetic acid (5‐HIAA) and of 5‐hydroxytryptamine (5‐HT) were estimated in left and right superior colliculi, thalami and hippocampi. 2. In rabbits exposed to such visual stimuli for 30‐60 min, there was an increase in the 5‐HIAA content of the colliculus contralateral to the stimulated retina which aberaged 17% (P = 0‐02), but no rise was seen if the exposure was shortened to 20 or prolonged to 80 min. At no time was there a difference in 5‐HIAA content between right and left thalamus or right and left hippocampus. 3. Stationary or strictly repetitive visual stimuli produced no difference between the 5‐HIAA content of left and right superior colliculus. 4. No difference in 5‐HT concentration between the two colliculi was found after any form of visual stimulation, nor did any changes occur in the other parts of the brain which were examined. 5. Irregular, prolonged visual stimualtion thus appears to activate tryptaminergic neurones terminating in the colliculi. The possibility is discussed that the 5‐HT released at this site might act as a brake to neuronal activity under conditions when habituation to the stimuli is not yet complete.
Mode of stimulation by aldosterone of the sodium efflux in barnacle muscle fibres: effects of ouabain, ethacrynic acid, diphenylhydantoin, (ATPMg)(2‐), adenine translocase inhibitors, pyruvate and oxythiamine.
Authors: Bittar E E , Tallitsch R B
Published: December 2014

1. A study has been made of the nature of the delayed stimulation caused by external aldosterone in barnacle fibres pre‐exposed to aldosterone. 2. (i) Microinjection of 0‐5 M‐ATPMg2‐ caused only a small but prompt rise in the Na efflux. (ii) Microinjection of 0‐5 M‐ATPMg2‐ followed by external application of 10(‐5)M aldosterone greatly augmented the magnitude of the delayed stimulation. The response was dose‐dependent, as well as dependent on the concentration of external K+ and H+, but not Na+, Ca2+ or Mg2+. (iii) External application of 10(‐5) M aldosterone for 30 min followed by its withdrawal from the bathing medium failed to bring about delayed stimulation. By contrast, fibres into which ATP had been injected showed delayed stimulation under these conditions. 3. Microinjection of actinomycin‐D or spironolactone SC‐14266 into fibres into which ATP had been injected followed by external application of aldosterone resulted in complete abolition of the delayed stimulation. 4. Delayed stimulation was reduced whether ATP had been injected or not by prior external application of 10(‐4)M ouabain or internal application of 8 x 10(‐2)M ethacrynic acid. It was completely abolished by prior application of ouabain externally and ethacrynic acid internally, or only 10(‐4)M diphenylhydantoin externally. 5. (i) Microinjection of atractyloside or bongkrekic acid caused a substantial fall in the resting Na efflux. Bonkrekic acid proved more powerful than atractyloside. Microinjection of 0‐05 M‐ATPMg2‐ into fibres poisoned with 2‐0 x 10(‐2)M bongkrekic acid completely restored the Na efflux.
Effect of renin‐angiotensin system on sodium intake.
Authors: Chiaraviglio E
Published: December 2014

1. Water and saline intake was measured in rats depleted of Na by I.P. dialysis. Na intake was prevented 180 min but not 60‐90 min after bilateral nephrectomy. Unilateral nephrectomy as well as ureteral ligature had no effect on Na intake. 2. Renin (3u.) injected I.P. re‐established the Na appetite abolished by nephrectomy. 3. Angiotensin I (5 ng) or II (5‐40 ng) injected into the 3rd ventricle, also restored the Na intake and this effect was dose‐dependent. 4. The angiotensin converting‐enzyme inhibitor Sq 20,881 (1 mg/kg) inhibited the effect of AI but not that of AII in restoring Na intake. 5. It is concluded that the kidneys might play a role in the regulation of Na intake through the renin‐angiotensin system.
The ionic basis of the resting potential and a slow depolarizing response in Rohon‐Beard neurones of Xenopus tadpoles.
Authors: Spitzer N C
Published: December 2014

1. Rohon‐Beard cells in the spinal cord of Xenopus laevis tadpoles have been studied in animals 4‐days to 2‐weeks‐old (Nieuwkoop & Faber, 1956, stages 45‐49). These neurones have an unusually large resting membrane potential of ‐88 mV, in Ringer solution containing 3‐0 mM K+. 2. Their resting potential (R..) depends on the concentration gradient of K+ across the cell membrane. These cells follow the prediction of the Nernst equation for a K+‐selective electrode, down to external K+ concentrations as low as 1‐0 mM (R.P. ‐118 mV). 3. The resting potentials of muscle cells in these animals exhibit the same dependence on external [K+], as has been shown previously. 4. Rohon‐Beard cells can be driven antidromically, bu stimulation of the anterior end of the spinal cord with brief current pulses through a suction electrode. Antidromic action potentials fail to invade the cell body with repeated stimulation at 1Hz. 5. Even when impulses fail to invade Rohon‐Beard somata, slow depolarizations can be produced by single shocks or trains of shocks which cause impulse activity in other neurones. The response can be observed to a single stimulus or to a train of stimuli. The magnitude of the depolarization is graded, depending on the number of stimuli and the frequency of stimulation. 6. Support is presented for the hypothesis that the slow depolarization in Rohon‐Beard cells is mediated by the release of K+ into their environment by the impulse activity of neighbouring neurones. The slow depolarization increases in solutions containing 1‐5 mM‐K+, and decreases in solutions containing 6‐0 mM‐K+. The changes are in quantitative agreement with those anticipated by theory. 7. The slow depolarization is unlikely to be due to a conductance change produced by a synaptic transmitter, since hyperpolarization and depolarization of the Rohon‐Beard cell with injected current do not change the amplitude of the response. Further, low Ca‐high Mg solutions which block neuromuscular transmission do not block the response. 8. The possible role of the slow depolarizing response in the physiological activity of these neurones is discussed.
Visual cortical cells: their developmental properties in normal and dark reared kittens.
Authors: Buisseret P , Imbert M
Published: December 2014

582 units were recorded in area 17 in twenty‐one normally reared kittens, and fourteen dark reared ones, aged between 8 and 42 days. 2. Four classes of neurones were defined: (a) non‐activable cells that cannot be excited by any peripheral stimulation; (b) non‐specific cells that are sensitive to a visual stimulus moving in any direction; (c) immature cells that are preferentially excited by a rectilinear stimulus but are unselective for its precise orientation; (d) specific cells that appear to be as selective for orientation as the simple or complex cells of the adult cat. 3. 23% of the cells presenting adult characteristics of specificity in terms of directionality and orientation are present in both the normally reared and in the dark reared kittens as soon as the first visual response (12 days) appears. 4. In normally reared kittens the proportion of specific cells increases with age, while that of the non‐specific cells decreases. 5. Up to 3 weeks of age there is no significant difference in the proportion of the different types of cells in the dark reared from the normal kittens. But thereafter in the dark reared kittens the specific cells tend to disappear while the non‐specific cells increase in number. 6. This confirms the view that cells with some highly specific response properties of the adult visual cortical neurones, especially in relation to orientation specificity, are present in the earliest stages in the absence of all visual experience. However, visual experience is necessary to maintain and develop these specific cells after the third week of post‐natal life.
The effect of external calcium and magnesium ions on the response of denervated muscle to acetylcholine.
Authors: Gordon T
Published: December 2014

1. The effect of external Ca and Mg on the membrane depolarization and contracture of rat denervated muscle in response to acetylcholine, ACh, was studied. 2. Raising external Ca concentration reduced the rate of rise and the amplitude of the ACh contracture, and prolonged its time course. 3. Increasing external Ca reduced the membrane depolarization in response to ACh. The dose increment required to elicit depolarization in high Ca concentration increased with external Ca, and was greater for depolarization than for contracture. 4. External Mg was less effect than Ca in reducing ACh depolarization but was more effective in reducing contracture. In contrast to Ca, Mg did not alter the time course of relaxation. 5. It is concluded that external Ca has two opposing effects on the ACh contracture: one of stabilizing the membrane and the other of increasing intracellular Ca concentration. External Mg may interfere with Ca influx and hence reduce contractility.
Temperature‐induced interconversion of alpha‐and beta‐adrenoceptors in the frog heart.
Authors: Kunos G , Nickerson M
Published: December 2014

1. The effect of ambient temperature on the properties of adrenoceptors mediating inotropic responses was assessed in isolated frog hearts on the basis of the effects and tissue uptake of alpha‐ and beta‐adrenoceptor antagonists. 2. At temperatures of 23degree C and above inotropic responses to adrenaline were antagonized by propranolol (0‐4‐4‐0muM), but were unaffected by phentolamine (26‐5muM) and were potentiated by phenoxybenzamine (POB) (0‐7‐29‐5muM). Below 17degree C the activity of propranolol was reduced at least tenfold, and the alpha‐adrenoceptor antagonists inhibited responses to both adrenaline and isoprenaline, but not those to CaCL2. 3. The responses of hearts exposed to POB at 14degree C and then tested, after thorough washing, at both 14 and 24degree C were similarly inhibited at both temperatures, i.e. the usual beta‐adrenoceptor response did not appear at the higher temperature. Conversely, exposure to POB at 24degree C produced only potentiation at both test temperatures. 4. Parallel to the reciprocal changes in their blocking actions, significantly more (14C)propranolol was retained by hearts exposed at high temperatures and significantly more (3H)POB was bound to the myocardium at low temperatures. Changes in binding and in the pharmaco logical effects of both blocking agents occurred entirely within a relatively narrow temperature range (17‐22degree C) Parallel to the change from alpha‐ to beta‐adrenoceptor characteristics with increasing temperature, the sensitivity of the hearts to adrenaline increased about tenfold. 5. Phentolamine (26‐5muM) effectively protected hearts from block by (3H)POB at 14degree C, unmasked a potentiation of responses to adrenaline equivalent to that produced by POB at 24degree C, and reduced binding of the label to approximately the level found in unprotected hearts exposed at the higher temperature. At 24degree C, phentolamine did not alter the potentiation produced by (3H)POB, and reduced binding only slightly. There was no significant temperature differential in the amount of (3H)POB bound in the presence of phentolamine. 6. The results presented indicate a close functional and, probably, morphological association of alpha‐ and beta‐adrenoceptors in the frog heart. It is suggested that the two classes of adrenoceptors may represent allosterie conformations of the same structure.
Unmyelinated fibres in the sacral 3 and caudal 1 ventral roots of the cat.
Authors: Applebaum M L , Clifton G L , Coggeshall R E , Coulter J D , Vance W H , Willis W D
Published: December 2014

1. 29% of the axons in the S3 and Ca 1 caudal ventral roots of the cat are unmyelinated. 2. Approximately one half of these unmyelinated axons survive in the proximal stump of a sectioned ventral root and are regarded as unmyelinated preganglionic efferents. 3. At least 27% of the preganglionic efferents in segments S3 and Ca 1 are unmyelinated. 4. The other half of the ventral root unmyelinated axons arise from dorsal root ganglion cells and survive in the distal stump of a sectioned ventral root. 5. The data in 4, combined with the receptive field data in our companion paper, show that these unmyelinated fibres are sensory. 6. Since 15% of the ventral root axons are sensory, the Law of Bell and Magendie cannot be regarded as an accurate description of the organization of these ventral roots.
Multiple light‐evoked conductance changes in the photoreceptors of Hermissenda crassicornis
Authors: Detwiler P. B.
Published: December 2014

1. Light responses were recorded from the photoreceptors of Hermissenda crassicornis. The response to a flash is a complex potential change involving an initial depolarization, a hyperpolarization, and a depolarizing tail. None of the phases of the response are due to synaptic interactions.

2. Polarization of the membrane by extrinsic current indicates that three separate conductance changes are associated with the response. The initial depolarization and hyperpolarization are accompanied by conductance increases and the tail with a conductance decrease. The initial depolarization has a positive reversal potential and the hyperpolarizing and tail phase have a reversal voltage more negative than resting potential.

3. The different processes that give rise to the conductance changes have similar spectral sensitivities but are affected unequally by light adaptation. Strong light adaptation reduced the depolarizing phases more than the hyperpolarizing phase, so that following an adapting stimulus the cell responded to illumination with a pure hyperpolarization (isolated hyperpolarization).

4. Removal of external Na+ ions greatly reduced the initial depolarization. In Na+‐free sea water the cell responds to dim flashes with a slow depolarization (isolated tail) that involves a conductance decrease, and has the same reversal potential as the hyperpolarizing response recorded from light adapted cells.

5. The amplitude of the isolated hyperpolarization and tail varied inversely with the external K+ concentration.

6. It is concluded that in Hermissenda photoreceptors light initiates processes that result in three distinct permeability changes. Following a brief flash there is: a rapid and transient increase in Na+ permeability that is responsible for the initial depolarization, a less rapid increase in K+ permeability that is responsible for the hyperpolarizing phase, and a delayed decrease in K+ permeability that gives rise to the depolarizing tail.
Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperaemia.
Authors: Kilbom A , Wennmalm A
Published: December 2014

1. The contribution of endogenously formed prostaglandins of the E series (PGE) to the development of reactive and functional hyperaemia was studied in the human forearm. 2. Forearm blood flow was recorded using venous occlusion plethysmography. The concentration of prostaglandin E‐like substances (PLS) in the venous effluent from the muscle was analysed using bio‐assay. For inhibition of PG biosynthesis, indomethacin (1‐25 mg/kg body weight) was administered. 3. Following 5 min of arterial occlusion, a marked hyperaemia developed during the next 150 sec. Indomethacin, while not affecting the resting arterial blood flow, significantly decreased the peak level as well as the duration of the hyperaemia. The total reactive hyperaemia was 25 ml./100 ml. tissue before, and 13 ml./100 ml. tissue after administration of indomethacin. 4. During sustained isometric forearm contraction, and following isometric and dynamic forearm muscle activity, a moderate hyperaemia was observed. This was significantly diminished when indomethacin had been administered, although not to the same extent as the reactive hyperaemia. The total hyperaemia in the absence and presence of indomethacin was 113 and 77 ml./100 ml. tissue, respectively, in connexion with isometric contraction and 206 and 120 ml./100 ml. tissue, respectively, following dynamic work. 5. The venous concentration of PLS was very low at rest. A significantly increased concentration was observed after ischaemia. This increased release of PLS was entirely suppressed by indomethacin. With the present assay method, muscular activity elicited no detectable change in the venous concentration of PLS. 6. It is concluded that reactive hyperaemia depends to a considerable extent on an intact PGE synthesis. It is furthermore suggested that endogenous PGE may contribute to the functional hyperaemia that appears during and after muscle activity.
Inputs from low threshold muscle and cutaneous afferents of hand and forearm to areas 3a and 3b of baboon's cerebral cortex.
Authors: Heath C J , Hore J , Phillips C G
Published: December 2014

The posterior wall of the central sulcus in forelimb area of SI has been expolred with extracellular micro‐electrodes in baboons lightyl anaesthetized with nitrous oxide and sodium thiopentone. 2. The excitatory responses of 130 single units to low intensity electrical stimulation of the deep radial (muscle) and the superficial radial (cutaneous) nerves have been investigated. 3. Units that responded only to muscle nerve stimulation were located in area 3a but overlapped into area 3b. Units that responded only to cutaneous nerve stimulation were found mainly in area 3b but a number occurred in area 3a. Units that responded to both muscle and nerve stimuli (convergent units) were found throughout area 3a and the rostral part of area 3b. 4. Latency analyses of all three response groups revealed a single population of units responding to low threshold muscle nerve stimulation (mean latency 8.5 msec), and both early and late populations responding to low threshold cutaneous nerve stimulation (mean latencies 9.5 and 13.6 msec respectively). A number of the convergent units had very similar latencies for both inputs. 5. Electrical stimulation within area 3a deminstrated a projection from areas 1 and 3b to area 3a; such a pathway may provide a route for excitation of the late skin population which was found mainly in area 3a. 6. In area 3a units commonly responded to light touch, local pressure or deep pressure but only rarely to movement of hairs. A number of the convergent units responded to natural stimulation of cutaneous receptors.
A comparison of the pepsin stimulating effects of secretin preparations.
Authors: Braganza J M , Howat H T , Kay G H
Published: December 2014

1. The peptic responses to Boots, GIH and synthetic secretins have been compared in fasting anaesthetized cats in which the pylorus and bile duct were occluded to prevent the release of duodenal hormones by acid and bile salts. A quantity of dilute acid introduced into the stomach at regular intervals ensured the total recovery of viscid secretions and preserved peptic activity. 2. The mean peak outputs of pepsin obtained in response to Boots secretin were significantly greater than the mean peak outputs of pepsin stimulated by equipotent doses of GIH secretin (4 Crick‐Harper‐Raper units of Boots secretin have been shown to stimulate a flow of juice and bicarbonate from the pancreas equal to that produced by 1 clinical unit of GIH secretin). The maximum output of pepsin stimulated by Boots secretin, 16 C.H.R. u./kg hr was 3 times the observed maximum output in response to the 4 times more potent dose of GIH secretin, 16 c.u./kg hr. The slopes of the log dose‐response lines were significantly different for these two products indicating that their modes of action in stimulating pepsin may not be identical. 3. The outputs of pepsin following GIH and synthetic secretin were similar. Both these secretins stimulated the secretion of pepsin when infused in doses which stimulated the pancreas supramaximally. The less pure product Boots secretin evoked significantly higher peptic responses at doses submaximal for pancreatic stimulation, suggesting that a substance other than secretin exists in Boots preparations which contributes significantly to the overall output of pepsin in response to this product. The peptic response which was accompanied by a slight increase in acid output, but without any increase in pancreatic lipolytic activity, was not inhibited by atropine. This substance which is not present in highly purified GIH secretin does not appear to be cholic acid, gastrin, pancreozymin, glucagon or insulin. 4. The possibility that a vasodilator substance is present in Boots secretin which by expanding the splanchnic bed increases the concentration of secretin at target sites in the stomach and pancreas seems unlikely, as the flow of pancreatic juice does not increase proportionately with the vast increase in pepsin. A vasodilator substance which specifically affects the gastric vasculature remains a theoretical but unlikely explanation for our observation.