bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of cyclic nucleotide levels in peripheral nerve without effect on resting or compound action potentials.
Authors: Horn J P , McAfee D A
Published: December 2014

1. Cyclic nucleotide levels and compound action potential magnitudes were measured in frog sciatic nerves following exposure to carbachol, isoprenaline and cyclic nucleotide related substances. 2. The resting cyclic AMP level was 2‐4 p‐mole/mg protein and the cyclic GMP level was 0‐27 p‐mole/mg protein in desheathed nerves. 3. Isoprenaline (100 micrometer) caused a twofold increase in cyclic AMP without affecting cyclic GMP levels. Carbachol (100 micrometer) caused a twofold increase in cyclic GMP without affecting cyclic AMP levels. 4. The phosphodiesterase inhibitor theophylline (5 mM) augmented both cyclic AMP and cyclic GMP. 5. The magnitude of the resting or compound action potential was not affected by isoprenaline, carbachol, or phosphodiesterase inhibitors. 6. The cyclic nucleotides and their butyryl derivatives did not affect the magnitude of the resting or compound action potential, either when applied alone or in the presence of a phosphodiesterase inhibitor. 7. In contrast to sympatic tissue we conclude that hormone mediated cyclic nucleotide metabolism in peripheral nerve is unrelated to control of axonal excitability.
Rapid desensitization of acetylcholine receptors of eel electroplaques following iontophoretic application of agonist compounds.
Authors: Del Castillo J , Webb G D
Published: December 2014

1. The electrical potential difference across the innervated membrane of the electroplaque of Electrophorus electricus was measured with an intracellular micro‐electrode while an extracellular double‐barrelled micropipette was used to apply acetylcholine and carbamylcholine iontophoretically very close to the point of insertion of the recording electrode. 2. The average depolarizing response to brief (several msec) pulses of carbamylcholine decayed 22 times more slowly than the response to acetylcholine. Treatment of the electroplaque with eserine or neostigmine prolonged the acetylcholine responses. 3. When a steady current of acetylcholine was applied for several seconds, the membrane first depolarized, then partially repolarized. Usually no repolarization was seen during long pulses of carbamylcholine or long pulses of acetylcholine in the presence of eserine or neostigmine. 4. During long conditioning pulses of acetylcholine or carbamylcholine, the responses to brief test pulses of acetylcholine showed a progressive decline in amplitude, but recovered after termination of the conditioning pulse. Desensitization half‐times as short as 0‐6 sec were observed, making these results similar to those obtained in the frog motor end‐plate.
Quantitative analysis of the velocity characteristics of optokinetic nystagmus and optokinetic after‐nystagmus
Authors: Cohen Bernard , Matsuo Victor , Raphan Theodore
Published: December 2014

1. Velocity characteristics of optokinetic nystagmus (OKN) and optokinetic after‐nystagmus (OKAN) induced by constant velocity full field rotation were studied in rhesus monkeys. A technique is described for estimating the dominant time constant of slow phase velocity curves and of monotonically changing data. Time constants obtained by this technique were used in formulating a model of the mechanism responsible for producing OKN and OKAN.

2. Slow phase velocity of optokinetic nystagmus in response to steps in stimulus velocity was shown to be composed of two components, a rapid rise, followed by a slower rise to a steady‐state value. Peak values of OKN slow phase velocity increased linearly with increases in stimulus velocity to 180°/sec. Maximum slow phase eye velocities in the monkey are 2‐3 times as great as in humans.

3. At the onset of OKAN, slow phase velocity falls by about 10‐20%, followed by a slower decline to zero. Peak OKAN slow phase velocities were linearly related to optokinetic stimulus velocities up to 90‐120°/sec. Above 120°/sec OKAN slow phase velocity saturated although OKN slow phase velocity continued to increase.

4. The charge and discharge characteristics of OKAN were studied. The OKAN mechanism charged in 5‐10 sec and discharged over 20‐60 sec in darkness. The time constants of decay in OKAN slow phase velocity decreased as stimulus velocities increased. They also decreased on repeated testing. In several monkeys there was a consistent difference in the rate of decay of OKAN slow phase velocity to the right and left.

5. Extended visual fixation discharged the activity responsible for producing OKAN. Short fixation times caused only a partial discharge of the OKAN mechanism. Following brief periods of fixation, OKAN resumed but with depressed slow phase velocities.

6. A model based on a state realisation of a peak detector was formulated which approximately reproduces the salient characteristics of OKN and OKAN. This model predicts the three dominant characteristics of OKAN: (1) charge over 5‐7 sec, (2) slow discharge in darkness, and (3) rapid discharge with visual fixation. With the addition of direct fast forward pathways, it also correctly predicts the rapid and slow rise in OKN. We postulate that OKAN is produced by a central integrator which is also active during OKN. Presumably this integrator acts to maximize velocities during OKN and to smooth and stabilize ocular following during movement of the visual surround.
Separation of sodium and calcium currents in the somatic membrane of mollusc neurones. With an Appendix by Yu A. Shakhovalov
Authors: Kostyuk P. G. , Krishtal O. A. , Shakhovalov Yu A.
Published: December 2014

1. Characteristics of the transmembrane ionic currents under controlled changes in ionic composition of extra‐ and intracellular medium were studied in isolated neurones from the ganglia of molluscs, Helix pomatia, Limnea stagnalis and Planorbis corneus. The neurones were investigated by a new technique which allows for dialysis of their interior and for clamping of the potential at the surface membrane without using micro‐electrodes.

2. Replacement of K ions by Tris inside the neurones eliminated the outward K current so that the actual time course of the inward current could be measured. The latter was separated into two additive components, one of which was carried by Na ions and the other one by Ca ions.

3. Both inward currents were unaltered by tetrodotoxin (TTX); however, Ca current could be separately blocked by externally applied Cd ions (Kd = 7·2 × 10−5
M) and by the use of fluoride as an intracellular anion.

4. No reversal of Na inward current could be achieved in neurones dialysed with Na‐free solution, indicating the absence of outward current carrying ions through the corresponding channels. With 5 m
M‐Na inside the cell, the equilibrium potential was close to the value predicted by the Nernst equilibrium.

5. A non‐specific outward current could be detected in K‐free cells at membrane potentials exceeding 20‐40 mV. Its time course was proportional to 1 — exp (—t/τns). Cd ions depressed this current. The presence of the non‐specific outward current made an exact measurement of the equilibrium potential for the Ca inward current impossible.

6. The kinetics of Na inward currents could be described by m3h and those of the Ca current by m2h law. The corresponding values for Vm = 0 are: τm(Na) = 1·1 ± 0·5 msec, τm(Ca) = 2·4 ± 1·0 msec, τh(Na) = 7·9 ± 2·0 msec. The inactivation of Ca current included two first‐order kinetic processes with τh1 = 50 ± 10 msec and τh = 320 ± 30 msec.

7. The data presented are considered to be a proof of the existence of separate systems of Na and Ca ion‐conducting channels in the nerve cell membrane.
Effects of calcium and calcium‐chelating agents on the inward and outward current in the membrane of mollusc neurones
Authors: Kostyuk P. G. , Krishtal O. A.
Published: December 2014

1. Effects of internal and external Ca and Ca‐chelating agents, EGTA and EDTA on transmembrane ionic currents were studied in isolated, internally dialysed neurones from the molluscs, Helix pomatia and Limnea stagnalis.

2. The possible pharmacological effect of internally applied EGTA was investigated on the background of constant free Ca concentration (5·3 × 10−9
M). EGTA had no effect on Ca and Na inward currents but considerably depressed the delayed K outward current. No effective removal of this action could be achieved by the elevation of intracellular free Ca.

3. In the absence of divalent cations in the external medium, EGTA (as well as EDTA) applied either intra‐ or extracellularly caused the appearance of a very large Na inward current with kinetics similar to those of Ca inward current and with the reversal potential around 10 mV. Effective concentrations of chelating agents were 0·1 m
M (extracellular) and 1·0 m
M (intracellular).

4. Increase in intracellular Ca in the absence of EGTA (by dialysis of the cell with Ca‐saturated solutions) did not produce any significant effect on the delayed K outward current. The small change observed in this current could be evaluated as a depression of maximum slope conductance and a shift to more negative membrane potential.

5. Ca inward current has been found extremely sensitive to internal Ca. 5·8 × 10−8
M of internal free Ca produced its complete depression. This effect was reversible. Na inward current could be inhibited with 3·5 × 10−7
M intracellular Ca.
Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise
Authors: Andersen Per , Henriksson Jan
Published: December 2014

1. Five subjects trained for 8 weeks on a bicycle ergometer for an average of 40 min/day, four times a week at a work load requiring 80% of the maximal oxygen uptake (V̇O2 max.). V̇O2 max. determinations were performed, and muscle biopsies from the quadriceps femoris muscle (vastus lateralis) were taken before, as well as repeatedly during, the training period. The muscle biopsies were histochemically stained for fibre‐types (myofibrillar ATPase) and capillaries (amylase‐PAS method), and analysed biochemically for succinate dehydrogenase and cytochrome oxidase activities.

2. The training programme resulted in a 16% increase in V̇O2 max., a 20% increase in capillary density, a 20% increase in mean fibre area, and an approximately 40% increase in the activities of succinate dehydrogenase and cytochrome oxidase.

3. The capillary supply to type I, IIA and IIB fibres, expressed as the mean number of capillaries in contact with each fibre‐type, relative to fibre‐type area, increased equally.

4. The present study shows that endurance training constitutes a powerful stimulus for capillary proliferation in human skeletal muscle.
Continuous direct measurement of intracellular chloride and pH in frog skeletal muscle
Authors: Bolton T. B. , Vaughan-Jones R. D.
Published: December 2014

1. Ion‐sensitive electrodes (made with a chloride‐sensitive ion‐exchange resin) were used to measure the internal chloride activity (aiCl) of frog sartorius fibres at 25° C.

2. The internal pH (pHi) of other sartorius fibres was measured with a recessed tip pH‐sensitive electrode (made with pH‐sensitive glass).

3. In normal bicarbonate‐free solution (containing 2·5 m
M potassium), the average chloride equilibrium potential, ECl (calculated from aiCl and the measured chloride activity of the external solution (aoCl) was 87·7 ± 1·7 mV (mean ±
S.E.; n = 16) in fibres where the average membrane potential, Em, was 88·3 ± 1·5 mV (mean ±
S.E.; n = 16). In experiments where aiCl was varied between about 1 and 10 m
M (which corresponds to values of Em between about ‐105 and ‐50 mV) ECl was within 1‐3 mV of Em at equilibrium. These measurements of aiCl were obtained from the potential difference between the chloride‐sensitive electrode and an intracellular indifferent micro‐electrode filled with potassium chloride. If a potassium sulphate‐filled indifferent micro‐electrode was used, then values of aiCl below about 5 m
M were erroneously high, probably due to interference from other sarcoplasmic ions at the indifferent electrode.

4. In solutions containing 15 m
M bicarbonate and gassed with 5% CO2, pHi was 6·9, corresponding to an internal bicarbonate concentration of 7·6 m
M. ECl measured in this solution was some 4 mV positive to Em. Most of the difference between ECl and Em could be ascribed to interference by sarcoplasmic bicarbonate on the basis of selectivity measurements of chloride against bicarbonate made on the ion‐exchange resin in the relevant range of aCl.

5. If bicarbonate/CO2 in the external solution was replaced by
HEPES/pure O2 at constant pH, then pHi rose from 6·88 ± 0·02 (mean ±
S.E.) to 7·05 ± 0·02. A change in external pH of 1 unit caused pHi to change by about 0·02 unit and the intracellular buffering power was calculated to be about 35.

6. In solution made hypertonic by the addition of sucrose, Em changed little or depolarized and ECl and Em remained close. In contrast, in solution made hypertonic by the addition of solid sodium chloride (high‐chloride solution) ECl became negative to Em. Conversely in low chloride solution ECl became positive to Em.

7. When the chloride permeability (PCl) was reduced by the use of acid solution, ECl moved positive to Em indicating an accumulation of internal chloride. When PCl was increased again by returning to more alkaline solution, Em depolarized to ECl.

8. The results are consistent with the existence of a small, active movement of chloride, the effects of which are normally obscured by large passive movements of chloride when PCl is large.
A ‘late supernormal period’ in the recovery of excitability following an action potential in muscle spindle and tendon organ receptors
Authors: Gregory J. E. , Harvey R. J. , Proske U.
Published: December 2014

1. Discharge patterns have been recorded from five types of stretch receptor; frog muscle spindles, lizard tendon organs, cat soleus tendon organs and primary and secondary endings of cat soleus muscle spindles.

2. The fully adapted discharge of each type of receptor is irregular, especially for frog spindles and primary endings of cat spindles as compared with the other three types (the ‘regularly firing’ receptors). Frog spindles and some cat spindle primary endings would maintain a discharge at very low mean rates (1/sec or less) while the remaining receptors would stop suddenly, as soon as their rate of discharge fell below a critical value characteristic for each individual ending.

3. This pattern of discharge suggests that there is a peak in the excitability of ‘regularly firing’ receptors at a time following a preceding impulse, which corresponds to the intervals between impulses at each particular receptor's slowest rate of maintained firing, and that the excitability subsequently falls again. Primary endings of cat muscle spindles also showed some evidence of such a ‘late supernormal period’, but frog spindles did not.

4. Direct evidence for the ‘late supernormal period’ was obtained from experiments in which a maintained discharge was restarted by an antidromic action potential in a receptor which had stopped firing, and to which had been applied a stretch just too small to restart the discharge.

5. It is shown in an Appendix that a model receptor in which the recovery of excitability following an impulse has a hyperbolic time course, and in which Gaussian distributed noise is superimposed on the generator potential, can have a discharge pattern very closely resembling that of a frog spindle (cf. Buller, 1965).

6. After addition of a late supernormal period to the model, its discharge pattern could mimic closely that of a lizard or cat tendon organ, or of a secondary ending of a cat spindle.
Changes in renal cyclic nucleotide content as a possible trigger to the initiation of compensatory renal hypertrophy in rats
Authors: Dicker S. E. , Greenbaum A. L.
Published: December 2014

1. Cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) and cyclic guanosine 3′, 5′‐monophosphate (cyclic GMP) have been estimated in the kidneys of rats.

2. Ten minutes after unilateral nephrectomy there was a threefold increase of cyclic GMP in the remaining kidney, which was accompanied by a moderate fall of cyclic AMP.

3. The changes in cyclic nucleotides in the remaining kidney after unilateral nephrectomy were of short duration.

4. When an anephric rat was cross‐circulated with a normal litter‐mate, there was an increase of cyclic GMP concentration in the kidneys of the latter, which reached its maximum 10 min after the establishment of the cross circulation.

5. In experiments where one kidney of a litter‐mate was transplanted to the neck of another rat, unilateral nephrectomy was not followed by changes of the level of cyclic nucleotides in either the transplanted or the remaining kidney. Bilateral nephrectomy, however, resulted in a marked increase of cyclic GMP in the transplanted kidney.

6. The clamping of the blood vessels to one kidney for periods up to 10 min had the same effect as unilateral nephrectomy on the concentration of cyclic GMP in the remaining kidney. When the clamp was removed and the circulation restored, the concentrations of cyclic nucleotides returned to preoperative levels in both kidneys.
The effect of calcium ions on the binomial parameters that control acetylcholine release during trains of nerve impulses at amphibian neuromuscular synapses
Authors: Bennett M. R. , Fisher C.
Published: December 2014

1. A study has been made of the effects of changing the external calcium concentration [Ca]o on the binomial parameters p and n that control the average quantal content (m̄) of the end‐plate potential (e.p.p.) during trains of nerve impulses at synapses in amphibian striated muscle.

2. In high external calcium concentrations (0·4 m
M ≤ [Ca]o < 1·0 m
M) the increase in m̄ of a test impulse following a conditioning impulse at different intervals (< 100 msec) was due to an increase in the number of quanta available for release, n; the increase in m̄ of successive e.p.p.s in a short high frequency train was primarily due to an increase in n.

3. In high external calcium concentrations (1·0 m
M ≤ [Ca]o < 10 m
M) there was a decrease in m̄ of a test impulse following a short high frequency conditioning train (4‐5 impulses, 20‐100 Hz) at different intervals (200 msec < 5 sec) and this was due to a decrease in the number of quanta available for release, n; in a long high frequency train (20 impulses, 20‐100 Hz) there was an increase in m̄ for the first few successive e.p.p.s followed by a depression of m̄ which eventually reached a steady state and these changes in m̄ were due to changes in n; the higher the frequency the greater was the depression in n during the steady‐state period.

4. In high calcium concentrations, the steady‐state m̄ reached in the first 20 impulses during continual stimulation at high frequency gave way to a decline in m̄ over several minutes until a new depressed steady‐state value of m̄ was reached and this was maintained during the longest periods of stimulation (30 min); this decline in m̄ was primarily due to a decline in the number of quanta available for release.

5. These changes in the number of quanta available for release during trains of impulses are predicted in terms of a hypothesis in which facilitation is due to the accumulation of a residual calcium‐receptor complex in the nerve terminal that determines the fraction of a pool of quanta which contributes to n, and depression is due to a decrease in the number of quanta in this pool.
Inhibitory processes underlying the directional specificity of simple, complex and hypercomplex cells in the cat's visual cortex
Authors: Sillito A. M.
Published: December 2014

1. The iontophoretic application of bicuculline, an antagonist of GABA, the putative inhibitory transmitter in the visual cortex, has been used to examine the contribution of post‐synaptic inhibitory processes to the directional selectivity of simple, complex and hypercomplex cells in the cat's striate cortex.

2. The directional selectivity of simple cells was significantly reduced or eliminated during the iontophoretic application of bicuculline. This supports the view that the selectivity is derived from the action of a GABA‐mediated post‐synaptic inhibitory input modifying their response to a non‐directionally specific excitatory input.

3. Complex cells were subdivided into three categories on the basis of the action of iontophoretically applied bicuculline on their directional selectivity, receptive field characteristics and distribution in terms of cortical layer. They are referred to as type ‘1’, ‘2’ and ‘3’ complex cells.

4. The directional specificity of type ‘1’ complex cells was eliminated during the iontophoretic application of bicuculline. It seems likely, therefore, that they receive a non‐directionally specific excitatory input and that, as for simple cells, the directional specificity derives from the action of a GABA‐mediated post‐synaptic inhibitory input. No type ‘1’ complex cells were recorded below layer IV.

5. The directional specificity of type ‘2’ complex cells was unaffected by the iontophoretic application of bicuculline, despite increases in response magnitude, a block of the action of iontophoretically applied GABA and, in some cases, changes in other receptive field properties. It is suggested that these cells receive a directionally specific excitatory input. The type ‘2’ complex cells were found both superficial and deep to layer IV with the majority in layer V.

6. Type ‘3’ complex cells appear to have very similar receptive field properties to those of the cells described by other workers as projecting to the superior colliculus. They were found predominantly in layer V. Their directional specificity was not eliminated by the iontophoretic application of bicuculline. However, they exhibited a powerful suppression of the resting discharge in response to stimulus motion in the non‐preferred direction. Iontophoretic application of ammonium ions revealed a small excitatory response in place of the suppression. It appears from these observations that the directional specificity of the type ‘3’ complex cells could be determined, at least in part, by an inhibitory process which is not GABA‐mediated.

7. The directional specificity of hypercomplex cells found in layers II and III was unaffected by the iontophoretic application of bicuculline, and they showed no suppression of their background discharge level in response to stimulus motion in the non‐preferred direction. This evidence is consistent with the view that they receive a directionally specific excitatory input.
Effects of 5‐hydrooxytryptamine on pial arteriolar calibre in anaesthetized cats
Authors: Harper A. Murray , MacKenzie Eric T.
Published: December 2014

1. The responses of individual pial arterioles and small arteries to perivascular injections of 5‐hydroxytryptamine were studied in anaesthetized cats.

2. Pial arteriolar calibre was measured by a television image‐splitting technique.

3. At normotension, the average response of pial vessels was dilatatory at injected 5‐hydroxytryptamine concentrations between 10−10 and 10−4
M.

4. These pial vascular changes were, however, dependent upon the resting vessel calibre: those arterioles < 70 μm dilated universally, whereas small arteries ≥ 200 μm in resting diameter tended to constrict in response to 5‐hydroxytryptamine.

5. The 5‐hydroxytryptamine‐induced dilatation of pial arterioles < 70 μm in resting calibre was directly dependent on mean arterial pressure, although no such relationship was observed with the larger cerebral vessels.

6. It is concluded that the specific cerebrovascular actions of 5‐hydroxytryptamine are largely tone‐dependent. The greater the resting tone of a pial arteriole, then the greater will be the tendency of that vessel to dilate in response to 5‐hydroxytryptamine, and vice versa.

7. The direct vascular actions of 5‐hydroxytryptamine are in contradistinction to the observed changes in cerebral tissue perfusion and it would therefore appear that the effects of this amine on cerebral metabolism and neuronal activity outweigh its cerebrovascular actions under physiological conditions.
Regeneration of rhodopsin in frog rod outer segments.
Authors: Azuma K , Azuma M , Sickel W
Published: December 2014

1. Bleaching/regeneration cycles were performed in perfused frog retina while the optical transmittance at suitable wave‐lengths was measured continously. Rhodopsin was identified from its spectral absorbance, its photosensitivity and from the kinetics of its regeneration. 2. In the absence of the pigment epithelium regeneration was complete when not more than 2‐5% of the rhodopsin initially present had been bleached. However, the cycles could be repeated to a total of regenerated rhodopsin exceeding that explicable on the utilization of stored chromophores. The rate of regeneration was fast, with 0‐12 min‐1 rate constant, following first order reaction kinetics. Under these conditions the cycle does not seem to involve stages beyond metarhodopsin II. With the moderate bleaching intensities used, half‐time 53 min, the Bunsen‐Roscoe law was obeyed up to 15 min, indicating a capacity for the photoproducts to be accomondated in situ for subsequent regeneration. 3. It is concluded that only substantial bleaches, which exceed that capacity, result in hydrolysed chromophores. These surplus chromophores become esterified and are temporarily taken up by the pigment epithelium to be re‐entered into the visual cycle as fast as they can be processed by the regenerative machinery of the rod outer segments.
Differential enhancement of early and late components of the cerebral somatosensory evoked potentials during forced‐paced cognitive tasks in man
Authors: Desmedt John E. , Robertson Donald
Published: December 2014

1. Cerebral potentials evoked by random sequences of electrical stimuli to four fingers were recorded in intact man performing selective attention tasks. Eye movements and other artifacts were excluded from the averaged traces. Different finger stimuli were designated as targets to be mentally counted in alternate runs of each experiment. The high mean random rate of stimuli (150/min) fully involved the processing capacities of the subject. Vigilance changes or differential expectancy effects were excluded by the reciprocal random design with four different sensory channels. Task‐related enhancements of somatosensory evoked potentials (s.e.p.) components were estimated by comparison with the s.e.p.s to physically identical finger stimuli recorded in runs when the subject attended signals in the opposite hand. The experimental design avoided subject's fatigue.

2. The primary s.e.p. components N20 and P45 were not significantly influenced and this excluded centrifugal gating of the corticipetal signals as a mechanism.

3. The earliest task‐related changes in s.e.p. occurred 55‐135 msec (mean 77·7 msec) after the target finger stimuli. In most cases the negative N140 component was markedly enhanced both for target signals and for non‐targets in the adjacent finger of the same hand. However, in several subjects the targets elicited a positive P100 component instead. Both N104 and P100 were larger at the contralateral parietal focus than ipsilaterally. They were definitely smaller at the vertex and frontal scalp locations.

4. Enhancements of N140 were not observed in similar random four‐finger experiments carried out at a 4 times slower mean rate, but they occurred in a bisensory paradigm with finger shocks and acoustic clicks at that slower rate.

5. A large positive P400 component was only elicited by target stimuli. Its voltage was maximum over the parietal region and was equal on both sides.

6. At least three categories of components can be differentiated in the cortical s.e.p. on the basis of their time domains (roughly 18‐70 msec, 70 to 200‐250 msec and over 200 msec after the finger stimuli), cerebral hemispheres topography and cognitive parameters. Verbal instructions defining specific perceptual tasks can to a large extent switch on and off the components of the second and third categories when the processing resources of motivated subjects are fully committed in a well designed forced paced paradigm. In certain individuals physiological evidence for a different ‘stimulus set’ processing of target (P100) and non‐target (N140) signals was documented for the first time.
Substance P and Renshaw cells: a new concept of inhibitory synaptic interactions.
Authors: Belcher G , Ryall R W
Published: December 2014

1. The actions of microelectrophoretically administered substance P on Renshaw cells in pentobarbitone anaesthetized cats were investigated. 2. The effects on spontaneous and synaptic firing and interactions with a number of other agents including acetylcholine, acetyl‐beta‐methylcholine, acidic amino acids, morphine, dihydro‐beta‐erythroidine and strychnine were studied in attempts to elucidate the mechanism of action of substance P. 3. Substance P usually selectively depressed the excitation by ACh, and also reduced submaximal synaptically evoked discharges which activate nicotinic receptors, but failed to modify excitation caused either by acetyl‐beta‐methylcholine, which activates muscarinic receptors, or excitation caused by glutamate or homocysteate. Substance P also depressed excitation by morphine which acted via the nicotinic receptors. 4. The inhibitory effect was not blocked by strychinine and was considered to be unlikely to be due to interaction between the polypeptide and either glycine or GABA receptors. 5. On some cells substance P caused excitation which was blocked by dihydro‐beta‐erythroidine. Mixed excitatory‐inhibitory effects were observed on some of these neurones. 6. The results are discussed in relation to the possibility that substance P could function as a synaptic inhibitory mediator with an unusual selectivity of action.
Uptake and loss of manganese from perfused frog ventricles.
Authors: Chapman R A , Ellis D
Published: December 2014

1. The uptake and loss of Mn has been studied in perfused isolated frog ventricles, at rest, during activity, in Na‐free fluid and in K‐rich fluid. 2. In normal Ringer the uptake of Mn with time is composed of two phases which can be interpreted as an initial saturating phase and a slower non‐saturating phase. The uptake in the resting heart is estimated to be 1.91 X 10(‐14) M.cm‐2.sec‐1, and the extra uptake associated with the action potential to be 6.90 X 10(‐13) M.cm‐2.beat‐1, when the heart is exposed to Ringer containing 8 mM‐Mn. 3. The washout of Mn from preloaded ventricles into Mn‐free Ringer is composed of at least two exponential phases. The slowest phase corresponding to a rate of Mn efflux of 1.72 X 10(‐14) M.cm‐2.sec‐1. 4. Mn uptake is not increased by exposure of the muscle to Na‐free fluids but is markedly increased by exposure to depolarizing fluids. 5. The Mn accumulating in the ventricles during a 7 1/2 min exposure to 8 mM‐Mn‐ringer with an elevated [K], increases with increasing [K]o to reach a peak at 75 mM‐K and then falls to quite a low value in 120 mM‐K. 6. The results are discussed in the light of the action of Mn ions on the contraction and the ionic currents of frog heart muscle.
Postural effects on muscle nerve sympathetic activity in man
Authors: Burke David , Sundlöf Göran , Wallin B. Gunnar
Published: December 2014

1. Pulse‐synchronous bursts of multi‐unit sympathetic activity (MSA) were recorded in peroneal muscle nerve fascicles in eight healthy subjects when lying, sitting and standing. The sympathetic activity was quantitated by counting the number of bursts in the mean voltage neurogram/min. Postural changes were analysed by considering the total activity to be a product of the number of bursts in relation to the number of heart beats (burst incidence) and the heart rate.

2. In lying there were large interindividual differences in total activity, but for all subjects the activity increased when going from lying to sitting and from sitting to standing. With a few exceptions the increase between the lying and sitting postures was associated with an increase in both burst incidence and heart rate whereas between the sitting and standing postures there was an increase in heart rate but on the average no change in burst incidence.

3. When going from lying to sitting or from sitting to standing the magnitude of the change in burst incidence was inversely related to the initial burst incidence so that subjects with low initial values usually showed greater increases in burst incidence than subjects with high initial values. Some subjects with high initial values decreased their burst incidence.

4. With changes in postures there was an inverse linear relationship between the fraction of the change in MSA associated with a change in burst incidence and the fraction associated with a change in heart rate. An increase in total activity could be obtained by changing only burst incidence, by increasing heart rate without changing burst incidence, or by appropriate changes in both parameters. The slope of the regression line was ‐0·53 indicating that for adequate postural compensation fewer additional bursts were required when the compensatory response involved an increase in heart rate rather than an increase in only burst incidence.

5. It is suggested that an impairment of the ability to regulate heart rate will make subjects with high burst incidence in the lying position orthostatically more vulnerable than those with low burst incidence.

6. Shortly after standing up one subject developed bradycardia and subsequently fainted. The nerve recording was maintained until the subject collapsed. During the initial bradycardia no sympathetic bursts occurred suggesting that the syncope was associated with an interruption of normal baroreflex feedback between blood pressure and sympathetic outflow.
Production of corticotrophin releasing hormone by the isolated hypothalamus of the rat.
Authors: Buckingham J C , Hodges J R
Published: December 2014

1. The ability of the rat hypothalamus to produce corticotrophin releasing hormone (CRH) in vitro was studied in the presence and absence of neurotransmitter substances, angiotensin and corticosterone. 2. Acetylcholine, 5‐hydroxytryptamine (5‐HT) and angiotensin II increased hypothalamic CRH release and content. 3. Noradrenaline and glycine decreased the spontaneous release of CRH from the hypothalamus but neither of these substances affected hypothalamic CRH content. 4. Dopamine, GABA, adrenaline, melatonin, histamine, glutamic acid and corticosterone did not affect the basal CRH activity of the hypothalamus in vitro. 5. Noradrenaline, GABA and corticosterone reduced the acetylcholine‐ and 5‐HT‐induced increases in the release of CRH from the hypothalamus. The rises in CRH content induced by acetylcholine and 5‐HT were also reduced by noradrenaline and GABA but increased by corticosterone. 6. The physiological significance of the results and the potential value of the technique are discussed.
Re‐innervation of guinea‐pig superior cervical ganglion cells by preganglionic fibres arising from different levels of the spinal cord
Authors: Njå Arild , Purves Dale
Published: December 2014

1. The ability of preganglionic axons to re‐establish their normal pattern of synaptic connexions with superior cervical ganglion cells has been studied after section of the cervical sympathetic trunk.

2. In vivo stimulation of the last cervical (C8) and the first seven thoracic ventral roots (T1—T7) 3‐4 months after section of the trunk produced end‐organ responses similar to those observed in normal animals.

3. The pattern of innervation of individual neurones, determined by intracellular recording of synaptic potentials 4‐9 months after cutting the sympathetic trunk, was also similar to that observed in normal neurones. Both normal and re‐innervated ganglion cells were contacted by pre‐ganglionic axons arising from C8 to T7, and each neurone was usually innervated by a contiguous subset of these segments.

4. Re‐innervated neurones, as normal cells, were typically dominated by the innervation from a particular spinal cord segment, with the adjacent segments contributing a synaptic influence that decreased as a function of distance from the dominant segment. This was true whether the amplitude of the post‐synaptic potential, or the estimated number of contributing axons, was used as the criterion of segmental dominance.

5. Re‐innervated neurones, however, showed some abnormalities. The average number of ventral roots contributing innervation to each neurone was reduced from 4·1 to 3·0, and discontinuities in the sequence of innervating segments were more frequent than in normal neurones. Moreover, fewer preganglionic axons contacted each neurone after regeneration.

6. A further difference between normal and re‐innervated neurones during the period covered by these experiments was that axons from the more caudal spinal cord segments were less successful in re‐establishing contacts with ganglion cells than those from the rostral segments. The more caudal the position of the preganglionic neurones, the more pronounced was this relative deficiency.

7. Although anomalies of ganglion cell innervation were apparent, the basis for the restoration of normal functional effects appears to be the re‐establishment of a pattern of innervation of individual neurones similar to that observed in normal ganglia.
Changes in motor commands, as shown by changes in perceived heaviness, during partial curarization and peripheral anaesthesia in man
Authors: Gandevia S. C. , McCloskey D. I.
Published: December 2014

1. The centrally generated ‘effort’ or direct voluntary command to motoneurones required to lift a weight was studied using a simple weight‐matching task when the muscles lifting a reference weight were weakened. This centrally generated input to motoneurones was increased when the lifting muscles were partially paralysed with curare or decamethonium as judged by the increased perceived heaviness of a reference weight lifted by the weakened muscles.

2. If subjects were asked simply to make matching isometric contractions when the lifting muscles were weakened the isometric tension produced by a weakened muscle was over‐estimated.

3. When subjects matched weights by flexing the distal joint of the thumb the perceived heaviness of a reference weight during a control partial curarization was compared with its perceived heaviness during a similar partial curarization when the thumb was also anaesthetized. At any level of maximal strength during curarization the perceived heaviness (which reflects the motor command to lifting motoneurones) was increased when the thumb was anaesthetized.

4. This increased voluntary command to lifting motoneurones may be required because automatic reflex assistance provided by apparent servo action from the long flexor of the thumb is suppressed by anaesthesia of the thumb (Marsden, Merton & Morton, 1971, 1973, 1976a; Dyhre‐Poulsen & Djørup, 1976).
The role of acetylcholine in the regulation of ion transport by rat colon mucosa
Authors: Browning J. G. , Hardcastle Jacqueline , Hardcastle P. T. , Sanford P. A.
Published: December 2014

1. Acetylcholine increases the potential difference across rat proximal colon both in vivo and in vitro.

2. There is a sigmoid relationship between the change in potential difference and the logarithm of the dose of acetylcholine. The dose—response curve is shifted to the left by neostigmine and to the right by atropine, suggesting that the action of acetylcholine is mediated by a muscarinic type of receptor.

3. The dose‐response curve for acetylcholine in vivo is not altered by the ganglion‐blocking agents hexamethonium and pentolinium, suggesting a direct effect of this transmitter on the colon.

4. Acetylcholine causes an increase in potential difference, a small decrease in resistance and hence a rise in the current generated by both normal and stripped everted sacs of rat colon.

5. In the absence of sodium, the calculated current change produced by acetylcholine is reduced, and the removal of chloride has a similar inhibitory effect. The absence of bicarbonate does not significantly affect the response.

6. Acetylcholine virtually abolished net sodium movement and induced net chloride secretion and these changes accounted for the increased short‐circuit current.

7. Acetylcholine had no effect on oxygen consumption by rings of colon.

8. Tracts staining for acetylcholinesterase were observed running from the submucous plexus towards the mucosal epithelium.

9. This study shows that acetylcholine can influence ion movement by rat colonic mucosa and suggests that the autonomic nervous system might be involved in the regulation of transport mechanisms in this tissue.
An analysis of the anatomical basis for the mechanical response to motor nerve stimulation of the rat vas deferens
Authors: Anton Patricia G. , Duncan Morag E. , McGrath J. C.
Published: December 2014

1. An anatomical basis was sought for the biphasic motor nerve response of the rat vas deferens. The motor nerve pathway to the tissue was stimulated at different points between the vertebral outflow and the intramural fibres, in the pithed rat and in isolated tissues, to examine the possibility of two anatomically separate groups of neurones. Different preparations of the isolated tissue were devised to detect whether different groups of smooth muscle fibres contributed to the two phases.

2. The fibres mediating both phases of the response arose from the upper lumbar vertebral outflows. Both phases were elicited by pre‐ or post‐ganglionic stimulation and could be depressed by hexamethonium. In the pithed rat or with hypogastric nerve stimulation in the isolated tissue, however, the initial ‘twitch’ phase was relatively resistant to such blockade.

3. When the rat vas deferens was perfused through the lumen in situ or in vitro, the perfusion pressure response to motor nerve stimulation exhibited two phases similar to those of the longitudinal contractile response.

4. Isolated rat vasa were bisected into portions, each of which was stimulated and longitudinal tension was recorded. The proportions of the two phases of the response varied along the length of the tissue. At the prostatic end the total response was relatively weak with a dominant ‘twitch’ and at the epididymal end the two phases were comparable in magnitude. The distribution of adrenergic nerve terminals within the muscle layers also varied along the length of the rat vas deferens.

5. The effects of drugs were investigated on the motor responses of the above preparations. The ‘twitch’ phase was relatively susceptible to blockade by reserpine and lysergic acid diethylamide and the ‘secondary’ phase to phentolamine with both equally sensitive to guanethidine. Each phase had similar susceptibilities to blockade irrespective of which part of the tissue was involved.

6. It was concluded that two types of nerve‐muscle transmission may be involved in the rat vas deferens with the proportion of each varying along the length of the tissue but both displaying pharmacological characteristics of adrenergic fibres.
Changes produced by chronic denervation in the temperature‐dependent isometric contractile characteristics of rat fast and slow twitch skeletal muscles.
Authors: Ranatunga K W
Published: December 2014

1. Influence of temperature (range 20‐35 degrees C) on the isometric contractile properties of normal and chronically denervated fast‐twitch extensor digitorum longus and slow‐twitch soleus muscles of the rat have been studied in vitro. 2. The times to peak twitch tension of denervated muscles were longer than those of normal in both types of muscle. The denervated muscles were, however, identifiable as 'fast‐twitch' or 'slow‐twitch' throughout the entire temperature range. 3. The twitch tension/tetanic tension ratios of the denervated muscles at 35 degrees C were significantly higher than those of the normal muscles. 4. The twitch tension of the normal extensor digitorum longus muscles increased whereas that of the normal soleus muscles decreased with cooling from 35 to 20 degrees C. Such a qualitative difference did not exist between the denervated extensor digitorum longus and soleus muscles. The twitch tensions of both denervated muscles decreased with cooling. 5. Cooling to 20 degrees C resulted in a greater fall in tetanic tension in the denervated than in the normal muscles.
Localization of sodium pump sites in cat salivary glands.
Authors: Bundgaard M , Møller M , Poulsen J H
Published: December 2014

1. Cat submandibular glands were perfused with Locke solution containing [3H]ouabain. In some experiments additional medium was given by retrograde intraductal injection. 2. [3H]ouabain binding sites were localized by light microscopical autoradiography and the findings compared with the electron micrographs. 3. The cells of the striated ducts were heavily labelled with [3H]ouabain, predominantly in the contraluminal parts. 4. At the acinar level moderate amounts of [3H]ouabain were found in relation to the plasma membranes of the demilunar cells. The central acinar cells were found to be virtually devoid of [3H]ouabain. 5. Electron microscopy revealed that the demilunar cells possessed long, tortuous intercellular spaces separated from the secretory canaliculi by junctional complexes. In contrast, the membranes between adjacent central acinar cells were fairly straight. 6. It is concluded that the striated ducts play a dominant role in the ductal reabsorption of sodium, and that the transport is probably mediated by a (Na+ + K+)‐activated ATPase. The findings on the acinar level are in agreement with the view that the primary saliva is formed predominantly by the demilunar cells. The role of a (Na+ + K+)‐activated ATPase in this process is unclear.
Permeability of the post‐synaptic membrane of an excitatory glutamate synapse to sodium and potassium.
Authors: Anwyl R
Published: December 2014

1. The changes in permeability of the post‐synaptic membrane at the insect skeletal neuromuscular junction caused by the excitatory transmitter and L‐glutamate have been studied using the voltage clamp technique. 2. The reversal potential (ER) of the excitatory post‐synaptic current and the glutamate current was +3 and +4 mV respectively. 3. ER of the synaptic current did not change when external K was altered between 0 and 20 mM, but did show a small positive shift in 40 mM external K. Reducing external Na to 1‐10 mM changes ER by 12‐18 mV. Reducing external Cl to to zero caused no change in ER. 4. It is proposed that the transmitter and L‐glutamate cause an increase in permeability to Na and K, but not to Cl. 5. In normal saline, the ratio of the permeability increase to Na and K (delta PNa/delta PK) is 0.9. 6. The changes in ER caused by altering external K were similar to those predicted by the Goldman‐Hodgkin‐Katz equation, assuming delta PNa/delta PK stays constant. 7. The changes in ER caused by alterations of external Na are much less than those predicted by the Goldman equation. 8. No glutamate current could be recorded in Na‐ and Ca‐free saline either at the resting potential or at depolarized or hyperpolarized membrane potentials. 9. It is proposed that the outward K current is dependent upon the inward Na current, and that the increase in K permeability is abolished in zero external Na.