bluuebunny/crossref_metadata_2025 huggingface dataset:
Life time and elementary conductance of the channels mediating the excitatory effects of acetylcholine in Aplysia neurones.
Authors: Ascher P , Marty A , Neild T O
Published: December 2014

1. The excitatory effects of acetylcholine (ACh) on an identified group of Aplysia neurones have been studied under voltage clamp in an attempt to measure the average life time. tau, of the channels opened by ACh and the elementary current, iel, flowing through these channels. The value of tau was determined both from spectral noise analysis and from current relaxations after voltage steps. Both methods lead to similar values. iel was calculated from the ratio of the variance of the ACh induced noise to the mean ACh induced current. 2. tau is increased by hyperpolarization, or by lowering the temperature. At 12 degrees C, tau = 27 msec AT ‐80 MV, tau = 17 msec at mV. tau is about 5 times smaller at 21 degrees C than at 12 degrees C. 3. iel increases linearly with hyperpolarization. At ‐80 mV, in Tris‐buffered sea water, the mean value of iel was 0.8 X 10)‐12) A at 12 degrees C. At 21 degrees C, this value was multiplied by 1.8. 4. The estimate of the ACh reversal potential Erev obtained by extrapolation of the relation between iel and the membrane potential V was + 30 mV. The estimate obtained from the analysis of the instantaneous current changes produced by voltage steps was + 15 mV. The difference between the two values appears to be due to the development of a K curent activated by the entry of Ca into the cell during the ACh response. This current introduces an error in opposite directions into the two estimates of Erev, which can therefore be assumed to be intermediate between + 15 and + 30 mV. An assumed value of + 20 mV yields an elementary conductance of 8 X 10(‐12) omega‐1 at 12 degrees C in Tris‐buffered sea water. 5. The total ACh induced current measured in steady‐state conditions increases more with hyperpolarization than does iel. The difference can be entirely accounted for by the fact that hyperpolarization increases tau. 6. When carbachol or tetramethylammonium is applied instead of ACh, the value of iel is identical to that found with ACh, but tau is slightly shorter (about 75%). 7. Inward ACh induced currents can still be observed in solutions where all Na has been replaced by Cs, Mg, or Ca. 8. iel increases when Na is replaced by Cs; it decreases when Na is replaced by Mg or Ca. In all Na‐free solutions, tau is larger than in Na sea water: the lengthening of tau is largest for Ca sea water, smallest for Cs sea water. An interpretation of these changes of gamma is proposed. This interpretation may also account for the voltage sensitivity of gamma in normal sea water. 9. Partial replacement of NaCl by TrisCl strikingly reduces the ACh induced current. gamma is not modified by Tris substitution, and the reduction of the total current is entirely accounted for by a steep decrease of iel. Tris does not seem to affect the pore opening and closing processes, but to block the ACh controlled channel.
The mode of action of antagonists of the excitatory response to acetylcholine in Aplysia neurones.
Authors: Ascher P , Marty A , Neild T O
Published: December 2014

1. The mode of action of various antagonists of acetylcholine (ACh) excitatory effects on Aplysia neurones was studied under voltage clamp. ACh was applied by iontophoresis whereas antagonists were applied in the bath. Tubocurarine and hexamethonium were the most thoroughly studied compounds. 2. The 'elementary current', calculated as the ratio of the variance of the ACh noise to the mean ACh induced current, was not modified by any of the antagonists tested. 3. The evolution of the ACh induced current after a voltage jump, which is normally described by a single exponential, was modified by all the antagonists tested. A common feature of the modified relaxations was the appearance, over a certain concentration range of the antagonist, of two successive and opposite exponential components. 4. The characteristics of the composite relaxations depend on the antagonist. For a given antagonist they vary with membrane potential, ACh concentration, and antagonist concentration. 5. The noise power spectra of the ACh induced current showed changes consistent with those of the relaxations. 6. In the absence of antagonists, the current induced by a steady application of ACh increases linearly with hyperpolarization. In the presence of antagonists, the I‐V curve shows a marked curvature, indicating a proportionally larger reduction of the ACh response at more negative membrane potentials. 7. The voltage sensitivity of the blocking action of hexamethonium and decamethonium is noticeably stronger than that of monovalent antagonists. 8. A model is proposed which accounts for the observed effects. It assumes that the antagonists studied bind perferentially to the 'activated' ACh‐receptor complex, and convert it to a non‐conducting state. Kinetic constants can be calculated for this reaction; e.g. for curare, at 12 degrees C and ‐80 mV, the dissociation and association constants were estimated at 0.1 sec‐1 and 4 X 10(5) M‐1 sec‐1. 9. Partial replacement of the extracellular Na by Tris modifies the relaxations observed in the presence of hexamethonium. Hexamethonium appears less effective in the presence of Tris, which supports the hypothesis that the binding site of the antagonists is linked to the ionic channel.
Combined voltage‐clamp and dialysis of Myxicola axons: behaviour of membrane asymmetry currents.
Authors: Bullock J O , Schauf C L
Published: December 2014

4. A new technique for the simultaneous internal dialysis and voltage‐clamp of Myxicola axons is described and shown to control the internal composition of the axon adequately. 2. The permeability ratio (PNa/PK) of the sodium channel is 15.5 in axons dialysed with sodium‐free solutions, somewhat higher than observed in perfused axons. 3. Asymmetry currents are easily recorded in dialysed Myxicola axons. At 4‐‐5 degrees C for pulse durations sufficiently short Qon = Qoff with a maximum charge displacement of 10 nC/cm2 and half the charge being displaced by a step to ‐32 mV. Maximum slope of the Q(V) curve is 15 mV/e‐fold change in charge displaced. The time constant tau on reaches a maximum of 325 microseconds at a potential of ‐23 mV. 4. The time course of sodium activation cannot be adequately accounted for by (Q/Q infinity) X using any single value of X for potentials between ‐40 and 40 MV. 5. Both asymmetry currents and INa are inactivated by the same amount when Myxicola axons are repetitively depolarized at frequencies from 0.1 to 50 Hz.
A transient release of potassium mediated by the action of substance P on rat parotid slices.
Authors: Friedman Z Y , Selinger Z
Published: December 2014

Substance P (a peptide of eleven amino acids) caused a Ca‐dependent release of K+ from rat parotid slices. The response to substance P differed from the alpha‐adrenergic and the cholinergic responses in that it was transient, of smaller extent, and was not inhibited by phentolamine and atropine. Substance P caused little, if any, amylase secretion. Successive additions of the peptide to the slice system maintained the effect of C+ release indicating that the transient response to a single addition of the peptide was due to inactivation of substance P and not due to a decline in the response of the tissue.
The role of calcium ions in tetanic and post‐tetanic increase of miniature end‐plate potential frequency.
Authors: Erulkar S D , Rahamimoff R
Published: December 2014

1. The role of Ca ions in transmitter release changes, during and after high frequency stimulation of the motor nerve (10‐‐100 Hz), was examined at the frog neuromuscular junction. 2. The stimulation‐induced changes in miniature end‐plate potential frequency (f) resembled the changes in end‐plate potential amplitude recently described by Magleby and Zengel (1975, 1976). 3. The effects of tetanic stimulation on f under inward electrochemical gradient for Ca ions were compared with those under reversed gradient and four differences were found: (a) The increase in f during the tetanus under reversed Ca gradient conditions is much smaller than with an inward Ca gradient. (b) The increase in f under reversed Ca gradient is preceded by a small decrease in f, whereas with an inward Ca gradient an immediate increase in f is observed. (c) After the termination of the tetanus with a reversed Ca gradient, there is a further increase in f, compared to a decrease with an inward Ca gradient. (d) The augmentation phase of post‐tetanic potentiation was practically abolished. 4. The experimental results are explained by assuming that high frequency nerve stimulation causes an increase in transmitter release by at least two distinct processes: influx of Ca ions through the presynaptic membrane and release of Ca ions from intracellular stores. It is suggested that Na ions couple nerve activity to intracellular release of Ca.
Effects of acetylcholine and parasympathetic nerve stimulation on membrane potential in quiescent guinea‐pig atria.
Authors: Glitsch H G , Pott L
Published: December 2014

1. In quiescent preparations of guinea‐pig right atria the action of ACh applied in the superfusion medium or released from parasympathetic nerve fibres was investigated by membrane potential measurements. 2. ACh‐containing solutions induced hyperpolarizations which did not show desensitization. 3. The relationship between hyperpolarization amplitude (corrected for non‐linear summation) and ACh concentration could formally be described by simple saturation kinetics with an apparent dissociation constant KACh = 1.3 x 10(‐6) M. 4. Stimulation with impulses subthreshold for myocardial excitation induced a membrane hyperpolarization by releasing ACh from post‐ganglionic parasympathetic nerve fibres. 5. The hyperpolarization reached maximum about 1 sec after the onset of stimulation. This slow development of hyperpolarization cannot be accounted for simply by diffusion from the site of release to the receptor site. 6. The hyperpolarization declined exponentially with a time constant of about 3 sec. In the presence of neostigmine (3 x 10(‐6) M) the hyperpolarization lasted for 2 min or more. It is concluded that the action of ACh is primarily terminated by enzymic hydrolysis.
The role of the autonomic nervous system in the control of glucagon, insulin and pancreatic polypeptide release from the pancreas.
Authors: Bloom S R , Edwards A V , Hardy R N
Published: December 2014

1. The mechanisms of release of pancreatic glucagon, insulin and pancreatic polypeptide (PP) in response to hypoxia and to 2‐deoxyglucose have been investigated in conscious calves 3‐5 weeks after birth. 2. A single injection of 2‐deoxyglucose (200 mg/kg I.V.) produced an abrupt rise in the concentrations of pancreatic glucagon, insulin and PP in the arterial plasma. The changes in plasma insulin and PP concentration were unaffected by prior section of the splanchnic nerves but were effectively abolished by atropine (0‐2 mg/kg I.V.). The rise in plasma pancreatic glucagon concentration was prevented in calves with cut splanchnic nerves that were given atropine but neither procedure alone suppressed the response. 3. 2‐deoxyglucose also caused a substantial increase in the output of glucocorticoids from the right adrenal gland together with a pronounced rise in adrenal blood flow. There was also a small but significant increase in catecholamine output from the adrenal medullae in these animals. 4. Intense hypoxia caused a pronounced increase in the concentration of PP in the arterial plasma. This was found to resemble the glucagon response to intense hypoxia in that it persisted in animals with cut splanchnic nerves that were given atropine. Less intense hypoxia caused a rise in plasma pancreatic glucagon concentration (but not PP) that was abolished by section of the splanchnic nerves. The changes in plasma insulin concentration in these experiments were consistent with the conclusion that they were secondary to changes in plasma glucose concentration. 5. It is concluded that pancreatic endocrine responses to both moderate hypoxia and 2‐deoxyglucose are mediated by the autonomic innervation.
Certain pharmacological characteristics of the release of pancreatic glucagon in response to stimulation of the splanchnic nerves.
Authors: Bloom S R , Edwards A V
Published: December 2014

1. The effect of alpha‐ and beta‐adrenoceptor blockade on the release of pancreatic glucagon, in response to stimulation of the peripheral ends of the splanchnic nerves has been examined in adrenalectomized calves 3‐5 weeks after birth. In addition, the effects of insulin, atropine and somatostatin on the glucagon response to splanchnic nerve stimulation have been assessed in adrenalectomized dogs. 2. In calves release of pancreatic glucagon in response to splanchnic nerve stimulation was not suppressed by phentolamine at a dose that effectively abolished alpha‐adrenergic inhibition of insulin release, or by propranolol, at a dose that completely eliminated the chronotropic action of the cardiac sympathetic innervation. 3. In dogs release of pancreatic glucagon in response to splanchnic nerve stimulation was not suppressed by atropine (0.2 mg/kg) or somatostatin, at a dose that caused a steady fall in the concentration of gastrin in the circulating plasma (0.5 microgram‐kg‐1 min‐1). Glucagon release was apparently potentiated by exogenous insulin (4.0 u./kg). 4. The results are discussed in relation to the findings of other workers and it is concluded that the precise mechanism whereby stimulation of the sympathetic innervation to the pancreas leads to secretion of glucagon merits more detailed investigation.
The pharmacological properties of some crustacean neuronal acetylcholine, gamma‐aminobutyric acid, and L‐glutamate responses.
Authors: Marder E , Paupardin-Tritsch D
Published: December 2014

1. A study was performed of the L‐glutamate, gamma‐aminobutyric acid (GABA), and acetylcholine (ACh) responses of cells in the stomatogastric ganglion of the crab, Cancer pagurus. 2. Ionophoretic or pressure application of L‐glutamate revealed three classes of responses: a K+‐dependent inhibition which reversed at 15‐20 mV more negative than the resting potential; a Cl‐ dependent inhibitory response which was at equilibrium at the resting potential; and a depolarizing response. 3. Ionophoretic or pressure applications of GABA likewise produced three kinds of responses: an increase in K+ conductance, an increase in Cl‐ conductance, and a depolarizing response. 4. Picrotoxin (10(‐6)‐10(‐5) M) was effective in blocking both the glutamate inhibitory responses. 10(‐4) M‐picrotoxin, which was necessary to produce a 50% block of the GABA‐K+‐dependent response, had no effect on the GABA‐Cl‐ response. 5. beta‐Guanidinopropionic acid (beta‐GP) was found to be an agonist for the GABA‐K+ response, but was ineffective in mimicking or blocking the GABA‐Cl‐ response. 6. ACh applications produced large depolarizing responses with a pharmacological profile similar to that of the nicotinic ganglionic response in vertebrates. 7. The muscarinic agonist, acetyl‐beta‐methyl choline (MeCh), produced depolarizations which decreased in amplitude as the membrane was hyperpolarized from ‐40 to ‐100 mV. Pilocarpine and oxotremorine produced changes in the endogenous activity of ganglionic neurones. 8. Implications of these results for the identification of synaptic transmitters in the somatogastric ganglion are discussed.
Potassium efflux in heart muscle during activity: extracellular accumulation and its implications.
Authors: Kline R P , Morad M
Published: December 2014

1. Extracellular K+ activity and transmembrane potential were simultaneously monitored with a K+‐selective micro‐electrode placed in the extracellular space and a standard KCl‐filled micro‐electrode in the intracellular space of the frog ventricular muscle. 2. K+ was found to accumulate during activity and had the approximate magnitude and time course to account for the measured membrane depolarization. 3. The magnitude of the K+ accumulation depended on the frequency of stimulation, diameter of the muscle and temperature of the bathing solution. 4. The time constants of accumulation and decay were dependent only on the diameter and the temperature of the strip. A Q10 of 2 was measured for the decay of accumulated K+. 5. Double barrelled K+‐electrodes were used to monitor the change in K+ activity accompanying a single action potential, since the reference barrel allowed for rapid compensation of the electrical potential fluctuations encountered in the subendothelial space. 6. K+ accumulated continuously during the plateau to a level which increased external K concentration by about 1 mM. This increase in the subendothelial space corresponds to about 1‐3 muA/cm2 or 10‐30 pmole/cm2‐sec‐1 of net K+ efflux. These values are at least an order of magnitude larger than required to discharge the membrane capacitance. 7. There is no direct relation between action potential duration and rate of development or magnitude of K+ accumulation during that action potential. 8. Increase in the external K concentration, while shortening the action potential and depolarizing the membrane, does not lead to an increased rate of accumulation of K+. The presence of Ni2+, on the other hand, prolongs the action potential and decreases the rate of K+ accumulation. 9. The results suggest that there is a substantial and continuous efflux of K+ during the action potential, which sums during rapid beating, resulting in membrane depolarization and alteration of action potential duration. The change in action potential duration in response to rate may be caused by alteration of EK in the local micro‐environments.
Tactile sensibility in the human hand: receptive field characteristics of mechanoreceptive units in the glabrous skin area.
Authors: Johansson R S
Published: December 2014

1. Impulses in tactile units innervating the glabrous skin of the hand recorded from the median nerve of adult human subjects. The recording electrodes which were made of tungsten were inserted percutaneously in the upper arm. 2. The units were classified on the basis of their sensitivity to sustained identation and to remote stimuli. Two types of rapidly adapting units and two types of slowly adapting units were found. In accordance with earlier reports they were denoted RA and PC units, and SA I and SA II units. 3. The sensitivity profiles of the receptive fields were analysed by measuring the extent of the receptive field as a function of the identation amplitude. 4. The RA and SA I units had receptive fields with several zones of maximal sensitivity distributed over an approximately circular or oval area typically covering five to ten papillary ridges. Within this area the sensitivity was high, whereas the sensitivity diminished steeply with increasing distance from this area. 5. The PC and SA II units had receptive fields with a single zone of maximal sensitivity and gentle continuous threshold increase outside this zone. 6. The relation between the identation amplitude and the receptive field size of a unit was described by a power function. The power exponent for the RA and SA I units was well below unity, whereas the PC and SA II units had exponenets greater than unity. The variation in exponent was very small among the RA and among the SA I units. Their average exponents were therefore regarded as characteristics of the unit type. 7. The SA II units were qualitatively studied with regard to their sensitivity to lateral skin stretch. Three different types of SA II units were described with regard to the directional pattern of this sensitivity. 8. The relation of the present findings to the problem of correlation between morphological structures of nerve end‐organs and physiologically defined unit types is considered. 9. Moreover, the findings, indicate that the RA and SA I units are well suited for the analysis of mechanical events on the skin surface with a high degree of spatial selectivity, whereas the PC and SA II units are suited for analysis of other mechanical events, e.g. vibration and various forms of tension in the skin and related tissues.
Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibres.
Authors: Kass R S , Tsien R W , Weingart R
Published: December 2014

1. Voltage clamp experiements studied the ionic basis of the strophathidin‐induced transient inward current (TI) in cardiac Purkinje fibres. 2. The reversal potential of TI (Erev) was determined in the presence of various bathing solutions. Erev averaged ‐‐5 m V in the standard modified Tyrode solution (Kass, Lederer, Tsien & Weingart, 1978). Erev was displaced toward more negative potentials when the external Na concentration (NaO) was reduced by replacement of NaCl with Tris Cl, choline Cl or sucrose. 3. A sudden reduction of NaO evoked a temporary increase in TI, followed after a few minutes by a sustained diminution. The initial increase was closely paralleled by an enhanced aftercontraction and could be explained by an indirect effect of NaO on internal Ca. The subsequent fall in TI amplitude could be accounted for by the reduced driving force, E‐‐Erev. 4. Erev was not significantly changed by replacing extracellular Cl with methyl‐sulphate, or by limited variations in external Ca (2.7‐‐16.2 mM) or external K (1‐‐8 MM). 5. These results are consistent with an increase in membrane permeability to Na and perhaps K. 6. TI was not directly affected by TTX, which blocks excitatory Na channels, or by Cs, which inhibits inwardly rectifying K channels. TI may be distinguished from the slow inward current by its kinetic, pharmacological and ionic properties. 7. TI might be carried by a pre‐existing ionic pathway such as the 'leak' channel which provides inward current underlying normal pace‐maker depolarization. Another possibility is that TI reflects Ca extrusion by an electrogenic Ca‐‐Na exchange.
Role of calcium in the fade of the potassium release response in the rat parotid gland.
Authors: Putney J W
Published: December 2014

1. The 86Rb release response in the parotid due to alpha‐adrenergic (epinephrine), muscarinic (carbachol) or peptide (Substance P) receptor activation exhibited 'fade': a return of efflux to control levels despite the continuing presence of agonist. 2. The time course of fade of the response to all three agonists was independent of the concentration of the agonist. 3. After fade was fully developed to one agonist, the response to an agonist acting on a different receptor was either absent or greatly diminished. 4. Removal of carbachol from muscarinic receptors with atropine 10 min prior to Substance P partially restored the ability of Substance P to produce a response. 5. Fade of the response with all three agonists was greatly retarded by the omission of Ca. 6. release of alpha‐amylase did not appear to fade following exposure to carbachol or Substance P. 7. It is concluded that the K+ release response may be inactivated with time due to diminution in responsiveness of the K+ channel to an increase in internal Ca2+.
Endotoxin fever in the new‐born guinea‐pig and the modulating effects of indomethacin and p‐chlorophenylalanine
Authors: Székely M.
Published: December 2014

1. At 30 °C ambient temperature E. coli endotoxin injected into the cerebral ventricles evokes a febrile response in 0‐3 day‐old guinea‐pigs. If the dose is sufficiently high, the fever is biphasic: two rising phases separated by a transient fall.

2. At 20 °C ambient temperature the change in body temperature after the endotoxin is still biphasic, but the transient fall is more pronounced and, finally, hypothermia develops. The relatively large surface area of the new‐born cannot explain, by itself, the hypothermia.

3. The phasic changes in body temperature following endotoxin administration are unlikely to be mediated by a single central factor, and a sequence of several factors could be postulated.

4. Indomethacin prevents the first‐phase febrile rise in body temperature, and also the consequent fall, but not the second‐phase rise.

5. p‐Chlorophenylalanine pre‐treatment prevents the transient fall only, it slightly increases the first‐phase rise and does not influence the second‐phase rise.

6. Prostaglandins and/or other derivatives of endogenous arachidonic acid in the brain might be responsible for the first rising phase of the endotoxin fever, and might also initiate a central serotonergic mechanism which, in turn, could lead to the transient falling phase between the two rising phases of fever. The mechanism of the second‐phase febrile rise in body temperature awaits some other explanation.
Regulation of glycolysis in intermittent exercise in man.
Authors: Essén B , Kaijser L
Published: December 2014

1. Seven healthy male volunteers performed intermittent exercise (15 sec work‐‐15 sec rest) at a high work load for 60 min and six subjects performed continuous exercise at an equally high load to exhaustion, which occurred after 4‐‐6 min. 2. Muscle biopsies were obtained from the lateral portion of the quadriceps muscle before intermittent exercise and after the end of a work period and the end of the subsequent rest period at 5, 15, 30 and 60 min of exercise, as well as before, immediately after and about 15, 30, 60 and 180 sec after continuous exercise. 3. The reduction in glycogen content was smaller and glucose‐6‐phosphate, glycerol‐1‐phosphate, lactate and malate contents were lower after both work and rest periods in intermittent compared with continuous exercise, indicating a lower rate of glycolysis. 4. ATP and CP levels had decreased at the end of work periods in intermittent exercise but increased to slightly below basal in the subsequent rest periods. A still larger decrease in ATP and CP levels was found after continuous exercise to exhaustion and a progressive increase occurred over the 3 min of recovery. 5. In each rest period during intermittent exercise citrate levels increased to reach above basal. They increased also in the recovery phase after continuous exercise, although more slowly. 6. The findings support the assumption that ATP, CP and citrate act as regulatory factors of glycolysis in human muscle by retarding certain rate limiting steps. The increase in G‐6‐P/F‐1‐6‐P2 ratio in rest periods of intermittent intense exercise and in the recovery phase of continuous intense exercise suggests that glycolysis is retarded at the phosphofructokinase reaction. 7. The factors mentioned may therefore contribute to the relative increase in lipid utilization during intense intermittent compared to continuous exercise.
The regulation of dopamine and noradrenaline in the rat carotid body and its modification by denervation and by hypoxia.
Authors: Hanbauer I , Hellstrom S
Published: December 2014

1. The mechanism whereby hypoxia lasting 20 min elicits a decrease in the dopamine content of rat carotid bodies was studied. 2. The concentrations of dopamine, noradrenaline, dihydroxyphenylacetic acid and homovanillic acid in carotid body were measured by a mass‐fragmentographic procedure. The turnover rate of dopamine was determined by measuring the elimination rate of dihydroxyphenylacetic acid immediately after inhibition of monoamine oxidase by injection of pargyline. The turnover rate of noradrenaline was derived from measurements of the rate of decline of noradrenaline content after injection of L‐methyl‐p‐tyrosine. 3. The results indicate that hypoxia increases the rate of dopamine release without changing its turnover rate thereby accounting for the decrease in dopamine content. The content and turnover rate of noradrenaline remained unchanged during exposure to hypoxia. 4. Neither the carotid sinus nerve nor the sympathetic innervation appeared to participate in the regulation of dopamine content or turnover rate in carotid bodies of rats either before or during hypoxia. 5. Since transection of the carotid sinus nerve or/and ganglionectomy failed to prevent the decrease of dopamine content caused by hypoxia, it is inferred that low arterial PO2 depletes dopamine stores independently of the above mentioned innervation.
Some properties of spinal gamma‐motoneurones in the cat, determined by micro‐electrode recording.
Authors: Kemm R E , Westbury D R
Published: December 2014

1. Micro‐electorde recordings were made from motoneurones in the lumbo‐sacral region of the cat spinal cord whose axonal conduction velocities were 10‐‐55 m/sec. Most of these may be presumed to be fusimotor in function. 2. Intracellular records from twelve gamma‐motoneurones revealed six with short (2‐‐4 msec) and six with long (30‐‐100 msec) duration after‐hyperpolarizations following an antidromically conducted action potential. 3. Using extracellular recording, the excitability of eighty‐nine other gamma‐motoneurones following an antidromic impulse was tested with a second antidromic action potential. In eighty‐four of these neurones, the minimum antidromic response interval was short, 1.5‐‐3.5 msec, implying that in most gamma‐motoneurones, after‐hyperpolarization was of limited effectiveness and of short duration. In the remaining five neurones, the minimum response interval was longer, 20‐‐80 msec. 4. There was a lack of monosynaptic excitation from group 1 afferent axons in the dorsal roots in eleven of the twelve motoneurones from which intracellular records were obtained. Polysynaptic excitation was commonly observed. 5. In these anaesthetized preparations, there was a lack of recurrent i.p.s.p.s even though such evidence of Renshaw inhibition could be found in the neighbouring alpha‐motoneurones. 6. The mean input resistance of gamma‐motoneurones was shown to be 1.55 Momega and the principal time constant 8.5 msec by passing hyperpolarizing current through the recording micro‐electrode in a bridge circuit. These values are open to error because of the small numbers of neurones investigated, and of the use of the single micro‐electrode method. 7. Depolarizing current passed through the recording micro‐electrode caused a maintained discharge of action potentials at a high rate. After‐hyperpolarization had little effect on discharge rate. The threshold for injected current to cause discharge was very low, and the discharge rate increased rapidly with the magnitude of the current. 8. These properties of gamma‐motoneurones arediscussed in relation to their function.
Evidence for anionic cation transport of lithium, sodium and potassium across the human erythrocyte membrane induced by divalent anions.
Authors: Becker B F , Duhm J
Published: December 2014

1. The passive net transport of Li+ and Na+ across the human red cell membrane was accelerated by the divalent anions carbonate, sulphite, oxalate, phosphite and malonate. Phthalate, maleate, sulphate and succinate were found additionally to stimulate downhill transport of K+. Marked differences in anion efficacy and selectivity were observed. 2. The effects of these ‘carbonate type’ anions were reversible and fully blocked by SITS, dipyridamole and other inhibitors of anion transfer. 3. Cation transport acceleration induced by the monovalent anions salicylate, benzoate, thiocyanate and 2,4‐dinitrophenol were inhibited by dipyridamole, but not affected by SITS. A great number of mono‐ and polyvalent anions were without detectable influence on Li+ transport. 4. Li+ net uptake induced by oxalate exhibited a pH dependence similar to that reported for halide self exchange. 5. Transport acceleration by carbonate type anions displayed a linear, 1:1 dependence on the concentrations of both the anion and the cation and was symmetric with respect to the two sides of the membrane. 6. It is concluded that the divalent carbonate type anions form singly charged, negative 1:1 ion pairs with the respective alkali metal cations, the ion pairs traversing the red cell membrane via the anion exchange pathway. This concept of anionic formation of some of the ion pairs considered. The relative efficacies and cation selectivities of polyvalent anions can largely be explained on the basis of electrostatic interactions governing ion pair formation. However, the chelating properties, structural flexibility, polarizability of the anions and the accessibility of the ion pairs to the anion exchange pathway need also be considered. 7. An exchange of NaCO‐3 ion pairs for internal HCO‐3 or Cl‐ is discussed as a possible mode of cellular pH regulation.
Stretch receptor control of renin release in perfused rat kidney: effect of high perfusate potassium.
Authors: Fray J C
Published: December 2014

1. These studies were conducted in the isolated perfused rat kidney to determine the effect of high perfusate K on the renin release induced by low perfusion pressure, renal vasoconstriction and isoprenaline, and to determine whether the magnitude of the K‐induced inhibition equalled that observed with renal vasodilation and high perfusion pressure. 2. Raising perfusate K concentration from 4.2 to 56 mM suppressed basal renin release, and the 56 mM‐K inhibited the renin release induced by low perfusion pressure (50 mmHg) or phenylephrine (0.83 micrometers). 3. Isoprenaline (0.79 micrometers) induced a marked increase in renin release; but high perfusate K, propranolol (0.28 mM), papaverine (0.39 mM), or high perfusion pressure (150 mmHg) inhibited this effect. 4. It is concluded that high perfusate K has a powerful inhibitory effect on the renin release induced by renal hypotension, vasoconstriction, and isoprenaline infusion, and that this effect may be mimicked by high perfusion pressure or renal vasodilation. A mechanism is proposed whereby these signals may inhibit renin release by depolarizing the juxtaglomerular granular cells.
The effect of sodium, calcium and metabolic inhibitors on calcium efflux from goldfish heart ventricles.
Authors: Busselen P , van Kerkhove E
Published: December 2014

1. 45Ca efflux and tissue Ca content were examined in goldfish ventricles under conditions known to affect cellular Ca movements. 2. EGTA or Ca‐EGTA was added to the washout solutions in sufficient concentration (10 mM) to avoid retardation of the apparent tissue 45Ca efflux by extracellular 45Ca binding or backflux. 3. After a variable initial increase, the cellular Ca content usually stabilizes within 60 min when ventricles are immersed in Li‐ or K‐substituted saline containing 1.8 mM Ca0 (under these conditions the internal Ca2+ concentration is below 10(‐5) M). 4. 45Ca efflux is maximally activated by external concentrations of Ca2+ as low as 10(‐6) M, in both Na‐containing and Na‐free saline. 5. 45Ca efflux decreases in Na‐free solutions. It is reactivated by Na‐saline. The effect of different external Na concentration on 45Ca efflux is comparable at external Ca2+ concentrations between 10(‐6) M and 2 x 10(‐3) M. 6. Reactivation of Ca efflux after Na0 readmission is inhibited by metabolic poisoning, or in the presence of 10 mM‐caffeine. Loading with 45Ca at very low external Ca2+ concentration prevents the inhibition of Ca efflux in Na‐free medium. 7. Caffeine (10 mM) produces contractions of about equla size when K‐depolarized preparations are immersed in either Na‐ or Li‐saline. At the same time there is a similar increase in 45Ca efflux in absence of Na0 and in its presence. 8. In the virtual absence of Ca2+0 (10(‐5) M‐Ca, 10(‐2) M‐EGTA) and Na+0, the residual 45Ca efflux is reversibly inhibited by cyanide (2 mM). 9. The results are roughly compatible with the general concept of ATP‐dependent Na‐Ca exchange in internal Ca2+ homeostasis. However, this hypothesis should probably be modified to account for the fact that under physiological concentrations Na+0 and Ca2+0 do not compete for activating 45Ca efflux. Metabolic products may be involved in Na0‐ and Ca0‐dependent Ca efflux. It is therefore not excluded that a Na‐independent active mechanism co‐operates with Na‐Ca exchange in Ca extrusion.
Displacement of activator thresholds in cardiac muscle by protons and calcium ions.
Authors: Brown R H , Noble D
Published: December 2014

1. The Na current threshold in sheep cardiac Purkinje fibres and in frog atrium is shifted in a positive direction by protons and Ca2+ ions. The titration curves for Purkinje fibres are consistent with a surface potential of ‐18 mV at pH 7.4 and 1.8 mM‐Ca. 2. In Purkinje fibres, the pacemaker K current activation curve, s infinity, is shifted in a positive direction by Ca2+ ions. The results are consistent with a surface potential of ‐16 mV in normal physiological solutions. 3. The results on s inifinity during pH changes are unexpected. As also shown by Van Bogaert, Vereecke & Carmeliet (1975) the voltage shifts are usually in the opposite direction to that expected from titration of external surface negative charges. 4. Acid solutions reduce the magnitude of iK2 when fully activated. Alkalinity has little effect on iK2. 5. Acidification and alkalinization are both capable of arresting spontaneous activity in Purkinje fibres. The effects of acidity are usually irreversible. The effects of alkalinity are reversible.
The baroreceptor input to cardiac vagal motoneurones
Authors: McAllen R. M. , Spyer K. M.
Published: December 2014

1. A study has been made of twenty‐three cardiac vagal motoneurones (c.v.m.s) in the nucleus ambiguus of chloralose‐anaesthetized cats.

2. C.v.m.s were identified as described previously (McAllen & Spyer, 1978). They were either spontaneously active (five units) or induced to fire by the ionophoresis of
DL‐homocysteic acid (DLH). Evidence is presented that above threshold, the DLH dose is not critical for the ability to show a baroreceptor influence.

3. The influence of the baroreceptors was determined by plotting pulse‐triggered histograms of c.v.m. activity. If the aortic baroreceptors were denervated, the pulse synchronous activity disappeared reversibly on carotid occlusion (eight out of eight cases). In five out of fifteen cells studied, when aortic baroreceptor pathways were intact, a small degree of cardiac modulation survived carotid occlusion.

4. Estimates of the central delay of the baroreceptor‐vagal reflex were made by timing the c.v.m. response to both electrical stimulation of the sinus nerve and natural baroreceptor stimulation. When both methods were used on individual units, electrical stimulation invariably gave shorter values. Natural stimulation gave values that fell into two ranges (20‐60 msec and 70‐110 msec), suggesting the involvement of two pathways.

5. Using higher currents, four c.v.m.s were induced to fire tonically during inspiration. Their activity in this phase showed a cardiac rhythm just as during expiration. Similarly, they responded to sinus nerve stimulation throughout the respiratory cycle.

6. This result is discussed in relation to the observation of others that the baroreceptor‐cardiac reflex is ineffective during inspiration. It is proposed that there is no need to invoke a ‘gate’ early in the pathway but that this phenomenon and the present observations are best explained by summation of influences at the c.v.m. cell membrane.
Pressure‐flow relationships and effects of noradrenaline and isoprenaline on the hepatic arterial and portal venous vascular beds of the dog.
Authors: Richardson P D , Withrington P G
Published: December 2014

1. The innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously, in situ. Under control conditions, the pressures, blood flows and calculated vascular resistances in these beds were similar to those previously reported in preparations where one bed was perfused alone. 2. The pressure‐flow curves in both the hepatic arterial and portal venous vascular beds were almost linear over the pressure ranges 30‐‐200 and 2.5‐‐12.0 mmHg respectively. There was no evidence of pressure‐induced autoregulation of flow in either circuit. 3. Increases in hepatic arterial blood flow and perfusion pressure were associated with a linearly related increase in hepatic portal vascular resistance. Occlusion of the hepatic artery caused a mean fall of 21.3% in portal vascular resistance. 4. Increases in hepatic portal blood flow and perfusion pressure were associated with a linearly related incease in hepatic arterial vascular resistance. Occlusion of the hepatic portal vein caused a mean fall of 16.0% in hepatic arterial vascular resistance. 5. Intra‐arterial injections of noradrenaline (0.1‐‐50 microgram) caused biphasic changes in hepatic arterial vascular resistance, and a rise in hepatic portal vascular resistance. Both hepatic vascular effects had a significantly shorter latency than any succeeding systemic cardiovascular effects. 6. Intraportal injections of noradrenaline (0.1‐‐50 microgram) caused hepatic portal vasoconstriction, and a biphasic change in the hepatic arterial resistance. Both of these effects had a significantly shorter latency than any succeeding systemic effects. 7. Intra‐arterial injections of isoprenaline (0.1‐‐10 microgram) caused dose‐dependent hepatic arterial vasodilatation but little change in portal vascular resistance. Intraportal isoprenaline caused little change in portal resistance but elicited dose‐dependent hepatic arterial vasodilatation. 8. The time courses of the responses to intra‐arterial and intraportal noradrenaline and isoprenaline indicate that the responses of the liver vascular bed which does not receive the direct injection were not due to recirculation of the vasoactive material. 9. It is postulated that vasoactive material injected into one inflow circuit of the liver elicits changes in the vascular resistance of the other inflow circuit by an intrahepatic effect.
Responses of olfactory receptor cells to step pulses of odour at different concentrations in the salamander.
Authors: Getchell T V , Shepherd G M
Published: December 2014

1. The response properties of single olfactory receptor cells in the salamander have been analysed in unitary recordings obtained with platinum‐black metal‐filled micro‐electrodes. 2. Stimulation has been carried out using an apparatus which delivers odour pulses of abrupt onset, steady plateau and abrupt termination. The pulses have been monitored near the site of stimulation on the olfactory epithelium during the experiments. 3. The main type of response was a discharge of impulses that was time locked to the stimulus pulse. The pattern of the responses consisted of a relatively brief latency of onset, a rapid rise in impulse frequency, a continuation of impulse firing during the plateau of the pulse, and an abrupt termination of the discharge correlated with the termination of the pulse. 4. There was a clear relationship between the receptor responses and odour concentration. In general, impulse firing frequency increased with increasing odour concentration. The firing frequency ranged from approximately 1‐‐3 impulses/sec at threshold, up to 20 impulses/sec at the highest concentration. 5. Two types of reduced impulse activity were observed. One occurred after the termination of the pulse and lasted 1‐‐3 sec; this was a common occurrence. The other type was seen during a pulse as a reduction of impulse activity compared to the background level; this type was rarely observed. 6. The receptor responses resembled those of mitral cells in the olfactory bulb to odour pulses in their sensitivity to odour concentration. They differed in that mitral cells show primary response categories consisting of brief excitation followed by suppression, and pure suppression, that are rarely seen at the receptor level. These differences may be ascribed to synaptic interactions in the olfactory bulb. 7. It is concluded that the majority of receptor cells have a stereotyped discharge response pattern and a systematic relation to odour concentration. These properties appear to reflect the simple time course of the odour pulses used in these experiments. This represents an initial step toward analysing olfactory coding at the receptor level using stimuli controlled in a manner similar to that used in other sensory systems.
Spatial summation in the receptive fields of simple cells in the cat's striate cortex.
Authors: Movshon J A , Thompson I D , Tolhurst D J
Published: December 2014

1. We have examined the responses of simple cells in the cat's atriate cortex to visual patterns that were designed to reveal the extent to which these cells may be considered to sum light‐evoked influences linearly across their receptive fields. We used one‐dimensional luminance‐modulated bars and grating as stimuli; their orientation was always the same as the preferred orientation of the neurone under study. The stimuli were presented on an oscilloscope screen by a digital computer, which also accumulated neuronal responses and controlled a randomized sequence of stimulus presentations. 2. The majority of simple cells respond to sinusoidal gratings that are moving or whose contrast is modulated in time in a manner consistent with the hypothesis that they have linear spatial summation. Their responses to moving gratings of all spatial frequencies are modulated in synchrony with the passage of the gratings' bars across their receptive fields, and they do not produce unmodulated responses even at the highest spatial frequencies. Many of these cells respond to temporally modulated stationary gratings simply by changing their response amplitude sinusoidally as the spatial phase of the grating the grating is varied. Nonetheless, their behavior appears to indicate linear spatial summation, since we show in an Appendix that the absence of a 'null' phase in a visual neurone need not indicate non‐linear spatial summation, and further that a linear neurone lacking a 'null' phase should give responses of the form that we have observed in this type of simple cell. 3. A minority of simple cells appears to have significant non‐linearities of spatial summation. These neurones respond to moving gratings of high spatial frequency with a partially or totally unmodulated elevation of firing rate. They have no 'null' phases when tested with stationary gratings, and reveal their non‐linearity by giving responses to gratings of some spatial phases that are composed partly or wholly of even harmonics of the stimulus frequency ('on‐off' responses). 4. We compared simple receptive fields with their sensitivity to sinusoidal gratings of different spatial frequencies. Qualitatively, the most sensitive subregions of simple cells' receptive fields are roughly the same width as the individual bars of the gratings to which they are most sensitive. Quantitatively, their receptive field profiles measured with thin stationary lines, agree well with predicted profiles derived by Fourier synthesis of their spatial frequency tuning curves.
T‐tubule swelling in hypertonic solutions: a freeze substitution study.
Authors: Franzini-Armstrong C , Heuser J E , Reese T S , Somlyo A P , Somlyo A V
Published: December 2014

Striated muscles from Rana pipiens have been exposed for variable periods of time to Ringer solutions made hypertonic by addition of either sucrose or sodium chloride. The muscles have been rapid‐frozen and then prepared for electron microscopy by either freeze‐substitution, freeze‐fracture or cryoultramicrotomy. The only compartment greatly affected by hypertonicity is the transverse tubular system, which is visibly swollen. None of the elements of the sarcoplasmic reticulum increase in size.
Inward calcium current in twitch muscle fibres of the frog.
Authors: Sanchez J A , Stefani E
Published: December 2014

1. Voltage clamp experiments using the three micro‐electrode voltage clamp technique were performed on sartorius muscles of the frog. 2. By blocking potassium currents with tetraethylammonium and replacing chloride ions with sulphate a slow inward current was detected. 3. The slow inward current is mainly carried by calcium, since it is abolished by cobalt and D‐600, it depends on external calcium, and is not affected by removing external sodium or by tetrodotoxin (TTX). 4. The slow inward current has a mean threshold of ‐40 mV, reaches a mean maximum value at ca. 0 mV of 81 microamperemetercm‐2 and has a mean reversal potential of +38 mV. 5. The calcium current is inactivated by the application of 2 sec conditioning prepulses according to a sigmoid curve with V(h) = ‐42 mV and k = 6.2 mV. 6. The slow time course of this calcium current makes it rather unlikely that it participates in contraction during a twitch, but it might be activated during long depolarizations as potassium contractures.