bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of electrogenic chloride secretion by prostaglandin E2 in guinea‐pig isolated gastric mucosa.
Authors: Bunce K T , Spraggs C F
Published: December 2014

1. The effects of prostaglandin E2 (PGE2) on ion transport were investigated in guinea‐pig isolated gastric mucosa. 2. Under resting conditions the mucosa produced a short‐circuit current (SCC), the majority of which could be attributed to electrogenic chloride secretion. This interpretation was confirmed by the dependence of the basal SCC on extracellular chloride, and inhibition by the chloride channel blocker, diphenylamine‐2‐carboxylate. The mucosa also exhibited low rates of acid secretion and of sodium and rubidium absorption. 3. PGE2 stimulated an increase in net chloride secretion which was more than sufficient to account for the concomitant increase in SCC. As with the basal SCC, the SCC response to PGE2 was chloride dependent and inhibited by diphenylamine‐2‐carboxylate. PGE2 also significantly increased acid secretion and net rubidium absorption, but these changes were not sufficient to account for SCC. 4. The H+‐K+‐ATPase inhibitor, omeprazole, inhibited basal and PGE2‐stimulated acid secretion, but did not modify the effects the PGE2 on net chloride secretion, SCC or conductance, suggesting that these effects of PGE2 were not related to changes in gastric acid secretion. 5. Both basal and PGE2‐stimulated SCC were dependent on extracellular sodium and inhibited by ouabain, indicating the importance of a sodium gradient and the Na+‐K+‐ATPase in maintaining the electrogenic properties of the mucosa. 6. These results are consistent with the view that PGE2 stimulates electrogenic chloride secretion in guinea‐pig gastric mucosa, and provide an ionic basis for the stimulation of secretion of sodium and chloride by prostaglandins observed in mammalian gastric mucosa in vivo.
A microelectrode study of the mechanisms of L‐lactate entry into and release from frog sartorius muscle.
Authors: Mason M J , Thomas R C
Published: December 2014

1. Changes in intracellular pH and intracellular anion levels were monitored in frog sartorius muscle fibres during exposure to extracellular L‐lactate, using ion‐sensitive microelectrodes. 2. Resting intracellular pH (pHi) in 20 mmol l‐1 HEPES buffer was 7.18 +/‐ 0.015 (S.E. of mean, n = 62). Exposure to an extracellular solution at pH 6.5 buffered with 20 mmol l‐1 3‐(N‐morpholino)propanesulphonic acid (MOPS) resulted in a slow intracellular acidification. 3. A reversible decrease in pHi and an increase in intracellular anion levels was observed when L‐lactate replaced chloride in equimolar amounts. The increase in intracellular anion level is consistent with intracellular accumulation of L‐lactate ion. 4. The rate and steady‐state change in pHi and anion level was a function of both extracellular pH and L‐lactate concentration, providing evidence for the coupled movement of lactate and proton equivalents. 5. The initial rate of uptake of L‐lactate, as measured by the change of pHi, was a non‐linear function of the extracellular L‐lactate concentration at extracellular pH 6.8 and 7.35. 6. No saturation was observed with concentrations of L‐lactate between 5 and 60 mmol l‐1 at pH 7.35 and 2.5 and 40 mmol l‐1 at pH 6.8. 7. The non‐linear relationship between the initial rate of change in pHi and extracellular L‐lactate was well fitted by a curve defining uptake as the sum of a carrier process displaying Michaelis‐Menten kinetics and a passive diffusion component. The apparent Km of the carrier was 10 mmol l‐1 at pHo 7.35 and 4 mmol l‐1 at pHo 6.8. 8. The initial rate of change of pHi in the presence of L‐lactate was significantly inhibited 39.1 +/‐ 6.2% by 2‐5 mmol l‐1 alpha‐cyano‐4‐hydroxycinnamate (n = 9; P less than 0.05, paired t test). 9. alpha‐Cyano‐4‐hydroxycinnamate had no detectable effect on the initial rate of change of pHi induced by propionate exposure. 10. The initial rate of change of pHi induced by L‐lactate was not affected by 20‐100 mumol l‐1 4‐acetamido‐4'‐isothiocyanostilbene‐2,2'‐disulphonic acid (SITS). 11. We conclude that L‐lactate crosses the membrane of the frog sartorius muscle with proton equivalents via (1) a carrier‐mediated process, and (2) passive diffusion of lactic acid. In the physiological range of L‐lactate concentrations and pH the transport process dominates.
Time course of transmitter action at the sympathetic neuroeffector junction in rodent vascular and non‐vascular smooth muscle.
Authors: Astrand P , Brock J A , Cunnane T C
Published: December 2014

1. Transmitter release from sympathetic postganglionic nerve terminals innervating the guinea‐pig and mouse vas deferens and the rat tail artery has been studied in vitro by focal extracellular recording with particular emphasis on the time course of transmitter action underlying the intracellular potential changes. 2. In the absence of stimulation, spontaneous excitatory junction currents (SEJCs) were recorded with amplitudes up to 500 microV and durations between 40 and 100 ms. SEJCs were unaffected by the competitive alpha‐adrenoceptor antagonist prazosin but blocked by alpha, beta‐methylene ATP which desensitizes P2‐purinoceptors. 3. During trains of supramaximal stimuli at 0.1‐4 Hz stimulus locked excitatory junction currents (EJCs) were evoked intermittently from the population of varicosities located under the suction electrode. 4. SEJCs were similar in amplitude and time course to EJCs evoked by low‐frequency stimulation in the same attachment in all three tissues. 5. SEJCs recorded using either a conventional AC amplifier or a patch clamp amplifier had the same time course. 6. These studies show that the time course of the current underlying the excitatory junction potential is brief and essentially the same in three different tissues. The prolonged time course of the excitatory junction potential in different tissues can be accounted for by the passive membrane properties.
Influence of endogenous opiates and cardiac afferents on renal nerve activity during haemorrhage in conscious rabbits.
Authors: Burke S L , Dorward P K
Published: December 2014

1. We investigated the effects of the opiate antagonist naloxone on changes in renal nerve activity and the renal sympathetic baroreflex during haemorrhage and whether they could be mimicked by blocking afferent input from cardiac receptors. 2. Renal nerve activity, arterial pressure and heart rate were recorded in conscious rabbits during blood loss of either 18 or 34‐40% of the blood volume. The renal sympathetic baroreflex was elicited by perivascular balloon‐induced changes in arterial pressure, before and at the end of haemorrhage. The experiment was repeated during intravenous naloxone infusion (4 mg kg‐1, then 0.12 mg kg‐1 min‐1), and after blocking afferent input from cardiac receptors (5% intra‐pericardial procaine). 3. Moderate haemorrhage elicited a rise in renal nerve activity and modest inhibition of the range of the renal sympathetic baroreflex. Severe haemorrhage triggered an abrupt fall in nerve activity and arterial pressure which was accompanied by strong inhibition of the baroreflex range and other curve parameters. There were minimal changes in the baroreceptor‐heart rate reflex. 4. Intravenous naloxone and pericardial procaine prevented the falls in renal nerve activity and pressure triggered by severe blood loss but did not affect the increase in activity elicited by moderate haemorrhage. Both drugs produced similar enhancement of the normovolaemic renal sympathetic baroreflex. Naloxone prevented the baroreflex inhibition elicited by both levels of haemorrhage while pericardial procaine prevented most (but not all) of the baroreflex inhibition seen during severe haemorrhage without affecting that found during moderate haemorrhage. 5. We conclude that cardiac receptors (probably ventricular baroreceptors) but not arterial baroreceptors have an opiate synapse on their reflex pathways to the renal nerve. A major part of the action of naloxone during haemorrhage can be explained by blockade of this type of synapse on baroreflex pathways to renal and probably other sympathetic vasoconstrictors. The presence of procaine‐resistant but naloxone‐sensitive effects during haemorrhage suggests a role for extra‐cardiac baroreceptors with opioid central nervous connections.
Estimating the timing of quantal releases during end‐plate currents at the frog neuromuscular junction.
Authors: Van der Kloot W
Published: December 2014

1. Following motor nerve stimulation there is a period of greatly enhanced quantal release, called the early release period or ERP (Barrett & Stevens, 1972b). Until now, measurements of the probability of quantal releases at different points in the ERP have come from experiments in which quantal output was greatly reduced, so that the time of release of individual quanta could be detected or so that the latency to the release of the first quantum could be measured. 2. A method has been developed to estimate the timing of quantal release during the ERP that can be used at much higher levels of quantal output. The assumption is made that each quantal release generates an end‐plate current (EPC) that rises instantaneously and then decays exponentially. The peak amplitude of the quantal currents and the time constant for their decay are measured from miniature end‐plate currents (MEPCs). Then a number of EPCs are averaged, and the times of release of the individual quanta during the ERP estimated by a simple mathematical method for deconvolution derived by Cohen, Van der Kloot & Attwell (1981). 3. The deconvolution method was tested using data from preparations in high‐Mg2+ low‐Ca2+ solution. One test was to reconstitute the averaged EPCs from the estimated times of quantal release and the quantal currents, by using Fourier convolution. The reconstructions fit well to the originals. 4. Reconstructions were also made from averaged MEPCs which do not rise instantaneously and the estimated times of quantal release.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of electric fields on transmembrane potential and excitability of turtle cerebellar Purkinje cells in vitro.
Authors: Chan C Y , Hounsgaard J , Nicholson C
Published: December 2014

1. Transmembrane potential (TMP) responses of Purkinje cells (PCs) in isolated turtle cerebellum to externally applied quasi‐steady‐state electric fields aligned with the dendritic axis were continuously measured using simultaneous intracellular and extracellular recording. TMP was obtained by subtraction of extracellular voltage fields from intracellular potential recorded at the same depth in the cerebellum. 2. The applied field changed the TMP with the polarity and amplitude dependent on the location on the PC membrane. This response at a given location increased linearly with external field up to a threshold level, beyond which active responses appeared. 3. The basic effect on TMP consisted of depolarization in the half of the dendrite towards which the fields were directed, and hyperpolarization in the other half. A pooled TMP depth‐profile shows a steady increase in polarization from the middle of the molecular layer towards each end. This profile correlates with that predicted from previously proposed cable models, giving them empirical support for the first time. 4. Active responses were triggered by the field‐induced depolarization. Tetrodotoxin (TTX)‐sensitive action potentials arose with the primary depolarization in the somatic region. Notched, Ca2+‐dependent action potentials arose with primary depolarization in the distal and mid‐dendritic regions. 5. A TTX‐sensitive voltage plateau was triggered by TMP‐depolarization in the proximal region. It in turn activated Na+‐spike trains. The frequency of spiking was proportional to the external field. At around 160 spikes/s, the Na+ spikes inactivated, and the TMP level rose to a more depolarized plateau. This latter plateau was also TTX‐sensitive. 6. During depolarization of the distal dendritic region, sometimes a Ca2+‐dependent plateau was observed. It appears to be associated with a small conductance increase. 7. Field‐induced hyperpolarization suppressed local spiking and voltage plateaux, but remote Ca2+ spikes with reduced amplitude appeared in recordings from the proximal region. Similarly, in the distal region, low‐amplitude, remote Na+ spikes and a Na+ plateau were observed superimposed on the hyperpolarizing baseline. The Na+ plateau apparently did not contribute to shunting of membrane currents in the distal dendrite. 8. The phase characteristics of the action potentials correlate with the modulation pattern noted in our extracellular study (Chan & Nicholson, 1986). Thus, the extracellular units ("giant spikes") were probably Na+ spikes activated in the soma and spread distally. Occasionally Ca2+ spikes, with a higher threshold, might also be activated to give dual‐phase response.(ABSTRACT TRUNCATED AT 400 WORDS)
Outward rectification of inhibitory postsynaptic currents in cultured rat hippocampal neurones.
Authors: Barker J L , Harrison N L
Published: December 2014

1. Inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) were recorded from cultured hippocampal neurones of the embryonic rat at 22 degrees C, using the whole‐cell patch‐clamp technique with a low‐Cl‐, 145 mM‐potassium gluconate solution in the patch pipette. Individual synaptic events were elicited at low frequency (0.05‐0.1 Hz) by stimulating a presynaptic neurone either by direct intracellular current injection, or by applying a brief pulse of L‐glutamate. 2. In target neurones voltage clamped at ‐40 mV, outwardly directed IPSCs of mean amplitude 0.23 nA were recorded. The IPSCs were depressed by the GABA antagonist bicuculline, and reversed polarity between ‐50 and ‐80 mV (mean ‐64 mV), as did current responses to gamma‐aminobutyric acid. The IPSPs and IPSCs reversed as a single phase; no bicuculline‐resistant ‘late’ synaptic event was observed. 3. The IPSCs had variable kinetics, with rise times between 1 and 5 ms (mean 2.9 ms) at ‐40 mV, and slower, monoexponential, decay phases (decay time constant, tau IPSC, 10‐40 ms at ‐40 mV). In some cells, tau IPSC clearly increased with depolarization. 4. The IPSC reversal potential was ‐64 +/‐ 9 mV (n = 23) under the experimental conditions used; this suggests that the synaptically activated channels are approximately 25 times more permeable to Cl‐ than to the gluconate anion. 5. The peak conductance associated with the IPSC showed outward rectification. The synaptic conductance measured at ‐40 mV was 1.7 times greater than that measured at ‐100 mV; at ‐20 mV, synaptic conductance was 2.5 times greater than at ‐100 mV. This outward rectification can be explained by a constant field model under these experimental conditions of asymmetric Cl‐ concentrations.
Excitation and sensitization of fine articular afferents from cat's knee joint by prostaglandin E2.
Authors: Schaible H G , Schmidt R F
Published: December 2014

1. In cats anaesthetized with alpha‐chloralose extracellular recordings were made from fine afferent units belonging to the medial articular nerve of the knee joint. The excitatory and sensitizing effects on articular afferents of prostaglandin E2 (PGE2) applied intra‐arterially close to the joint were examined. 2. Bolus injections of PGE2 doses of 0.03‐30 micrograms excited about 60% of both the group III (conduction velocity 2.5‐20 m/s) and the group IV units (conduction velocity less than 2.5 m/s). The duration and size of the responses were dose dependent consisting in most cases of low‐frequency discharges which lasted up to several minutes. Excitation was found among afferents with low and high mechanosensitivity. 3. Among the group III units PGE2 sensitized 64% for their responses to movements and 50% for their responses to bradykinin (applied intra‐arterially close to the joint). Sensitization did not depend on the mechanical threshold previous to chemical stimulation. Among the group IV units PGE2 sensitized only 25% for their responses to movements but 75% for their reactions to bradykinin. In group IV fibres a low mechanical threshold predisposed for sensitization to movements and a higher threshold for sensitization to bradykinin. 4. Some units were sensitized and excited, others were either sensitized or excited and some units were not affected by PGE2. We conclude that PGE2 induces in a large proportion of fine articular afferents of normal joints discharges which are similar to those induced by an experimental inflammation. Thus PGE2 may be an inflammatory mediator which has a major role in the generation of the afferent activity developing in the course of an arthritis.
Control of light‐sensitive current in salamander rods.
Authors: Hodgkin A L , Nunn B J
Published: December 2014

1. The exponential decline of light‐sensitive current seen after switch from Na+ to Li+ in the presence of Ca2+ probably depends on the activity of the phosphodiesterase (PDE) which hydrolyses cyclic GMP. 2. This probability is supported by experiments with suction electrodes which show that in toad and salamander rods the rate constant, b, of the exponential decline of current was increased at least 10‐fold by moderate light intensities and decreased about 10‐fold by 3‐isobutyl‐1‐methylxanthine (IBMX), an inhibitor of PDE. 3. The rate constant b is about 3 times more sensitive to weak lights or to IBMX than the membrane current. This may be explained by a feed‐back involving calcium ions which tends to hold current constant, perhaps by calcium inhibition of guanylate cyclase. 4. The time course of b, which probably represents the changes in PDE activity, was measured by switching from Na+ to Li+ at various times after a flash. The results suggest that a moderate flash (140 Rh) increased b about 7 times in 0.5 s and that b then declined with a time constant of 1.5‐2 s. 5. Extrapolated values of the parameter b suggest that strong flashes (5000‐10,000 Rh) increased b from 1 s‐1 in the dark to perhaps 60 s‐1 and that b continued to increase with flash strength for several log units after the current had reached saturation. 6. The observations in 4 and 5 fit well with the idea that b is related to PDE activity and that changes in the latter are sufficient to account for the rising phase of the flash response. 7. After a flash the light‐sensitive current recovers much more rapidly than the time constant b‐1, a discrepancy which is explained if a light flash causes a delayed increase in guanylate cyclase activity. 8. The apparent delayed increase in cyclase activation is consistent with an inhibitory effect of [Ca2+]i which is reduced when calcium is pumped out during the plateau of the response. 9. Experiments in which pulses of IBMX were applied at different times during a flash response support the idea that a flash causes a delayed increase in the rate of supply of cyclic GMP. Quantitative analysis of these and other tests with IBMX gave rate constants similar to those obtained by the Na+‐‐‐‐Li+ method.
Role of alpha‐adrenoceptors in constrictor responses of rat, guinea‐pig and rabbit small arteries to neural activation.
Authors: Angus J A , Broughton A , Mulvany M J
Published: December 2014

1. We have investigated the adrenoceptors mediating the force and electrical responses of rat mesenteric small arteries (i.d. 100‐300 microns). Some mechanical experiments were also performed using guinea‐pig and rabbit mesenteric small arteries. 2. Vessels were mounted on an isometric myograph and stimulated either with short (3 s) trains of electric field stimuli (ca. 0.2 ms pulse width) at 25 Hz (nerve stimulation) or with 10 microM‐exogenous noradrenaline. 3. Nerve stimulation caused a force response equal to ca. 40% of the response to exogenous noradrenaline and, in the rat vessels, excitatory junction potentials (EJPs), which normally summated to give a depolarization of ca. 10 mV (although action potentials were sometimes seen). 4. Almost complete and reversible inhibition of the force responses of all vessels to both exogenous noradrenaline and to nerve stimulation was obtained using prazosin (0.1 microM) or phentolamine (1 microM). 5. Irreversible blockade of alpha 2‐receptors enhanced the force response of all vessels to nerve stimulation by ca. 50%, but did not affect the force response of rat and guinea‐pig vessels to exogenous noradrenaline. In the rabbit vessels this force response was abolished by alpha 2‐blockade. 6. Following alpha 2‐blockade, in the rat vessels the alpha‐antagonists prazosin (0.1 microM), phentolamine (0.1 microM), phenoxybenzamine (0.01 microM) and benextramine (10 microM) all totally abolished the force response to exogenous noradrenaline, and inhibited the response to nerve stimulation by at least 80%. Similar effects of phentolamine were seen in the guinea‐pig and, for the response to nerve stimulation, in the rabbit vessels. 7. In the rat vessels, alpha‐adrenoceptor antagonists did not affect the EJPs, but did inhibit the small depolarization which resulted from several seconds of nerve stimulation. The ATP analogue alpha, beta‐methylene‐ATP (3 microM) abolished the EJPs, but only slightly reduced the force responses. 8. The results suggest that the force response to nerve stimulation of the rat mesenteric small arteries is mediated primarily through alpha‐adrenoceptors, but also to a small degree through non‐alpha‐adrenoceptors, possibly ATP receptors.
The renotrophic factor, a persistent stimulus that crosses the placenta in mice.
Authors: Averbukh Z , Bogin E , Cohn M , Goren E , Modai D , Rosenmann E , Weissgarten J
Published: December 2014

1. Twenty 7‐week female mice underwent right nephrectomy and twenty others were sham operated. A week later all animals were made pregnant. Pregnancy was repeated five more times consecutively and various renal parameters were assessed in the pups. 2. Fractional fresh kidney weight (relative to body weight) was significantly increased in the pups of nephrectomized mothers while percentage renal water and protein content expressed as mg/g kidney weight were not statistically different in the two groups of pups. Thus dry kidney weight and amount of protein per kidney were increased in the experimental group. This was true for the newborns of all six pregnancies. 3. Renal morphometric studies performed in newborns of first pregnancies showed that the mean number of glomeruli per microscopic field, mean fractional cumulative glomerular area (relative to microscopic field area) and the mean number of cells per glomerulus were significantly greater in the experimental group. Mean glomerular radius was not statistically different in the two groups. 4. The results indicate that: (1) the renotrophic factor(s) crosses the placenta in mice; (2) its activity in maternal circulation following uninephrectomy is sustained for a relatively long period; and (3) fetal response to enhanced maternal renotrophin stimulation consists of increased renal dry weight and renal protein, formation of super‐physiological numbers of glomeruli and cellular hyperplasia of the glomeruli.
Binocular co‐ordination of human vertical saccadic eye movements.
Authors: Collewijn H , Erkelens C J , Steinman R M
Published: December 2014

1. The binocular co‐ordination of human vertical saccades was analysed systematically over the full oculomotor range, with a precise and accurate scleral sensor coil technique. Effects of amplitude (1.25‐70 deg), direction (upward vs. downward and centripetal vs. centrifugal), as well as position (upper or lower sector of vertical oculomotor range), were investigated systematically in three subjects. 2. All saccades were made voluntarily between continuously presented pairs of targets, which subtended equal angles of target vergence. 3. Vertical saccades were less accurate than horizontal saccades (as described by Collewijn, Erkelens & Steinman, 1988). For target distances between 10 and 70 deg, upward saccades undershot the target by about 10%, whereas downward saccades tended to overshoot the target. Downward saccades were about 1.5 deg larger than upward saccades between the same targets. 4. Peak velocities continued to increase monotonically with saccadic amplitude up to 513 +/‐ 27 (S.D.) deg/s for 70 deg saccades; a distinct asymptotic level was not reached. 5. Velocity profiles of upward and downward saccades, made symmetrically about the primary (straight‐ahead) position, were very similar for amplitudes up to 30 deg. At larger amplitudes, velocity profiles of upward saccades remained single peaked, whereas those of downward saccades invariably developed a second velocity peak. 6. Parameters of upward saccades depended heavily on the position of the eye. In the upper oculomotor range such saccades had lower maximum speeds, longer durations, and were more skewed than similar saccades in the lower oculomotor range (below primary). Downward saccades were almost independent of eye position. 7. Vertical eye movements during vertical saccades were virtually identical in the two eyes. In contrast, disjunctive horizontal components were systematically present. Upward saccades, at all amplitudes, were associated with diverging eye movements. Converging eye movements occurred during downward saccades. These systematic effects suggest that the vergence subsystem is not turned off during saccades. 8. These changes in vergence were followed by converging horizontal post‐saccadic drift after upward saccades, and in diverging horizontal drift after downward saccades.(ABSTRACT TRUNCATED AT 400 WORDS)
The physiological basis of heterochromatic flicker photometry demonstrated in the ganglion cells of the macaque retina.
Authors: Lee B B , Martin P R , Valberg A
Published: December 2014

1. Heterochromatic flicker photometry is a way of measuring the spectral sensitivity of the human eye. Two lights of different colour are sinusoidally alternated at, typically, 10‐20 Hz, and their relative intensities adjusted by the observer until the sensation of flicker is minimized. This technique has been used to define the human photopic luminosity, or V lambda, function on which photometry is based. 2. We have studied the responses of macaque retinal ganglion cells using this stimulus paradigm. The responses of the phasic ganglion cells go through a minimum at relative radiances very similar to that predicted from the V lambda function. At this point, defined as equal luminance, an abrupt change in response phase was observed. A small residual response at twice the flicker frequency was apparent under some conditions. 3. The spectral sensitivity of parafoveal phasic cells measured in this way corresponded very closely to that of human observers minimizing flicker on the same apparatus. 4. Minima in phasic cell activity were independent of flicker frequency, as is the case in the psychophysical task. 5. The response minima of phasic cells obey the laws of additivity and transitivity which are important characteristics of heterochromatic flicker photometry. 6. As the relative intensities of the lights were altered responses of tonic, spectrally opponent cells usually underwent a gradual phase change with vigorous responses at equal luminance. The responses of tonic cells treated individually or as a population could not be related to the V lambda function in any meaningful way. 7. We conclude that the phasic, magnocellular cell system of the primate visual pathway underlies performance in the psychophysical task of heterochromatic flicker photometry. It is likely that other tasks in which spectral sensitivity conforms to the V lambda function also rely on this cell system.
Dose‐response effects of pressor doses of arginine vasopressin on renal haemodynamics in the rat.
Authors: McVicar A J
Published: December 2014

1. Dose‐response effects of arginine vasopressin on renal haemodynamics were studied in conscious and in pentobarbitone‐anaesthetized rats infused with 77 mM‐NaCl at 5.2 and 2.6 ml h‐1 respectively. 2. Vasopressin at 0.8 pmol h‐1 (100 g body weight)‐1 did not have a significant effect on arterial blood pressure in conscious or anaesthetized rats. Increasing the dose to 2.5 pmol h‐1 (100 g body weight)‐1 induced a pressor effect in conscious rats but not in anaesthetized rats. A pressor response was observed in the latter at a dose of 10 pmol h‐1 (100 g body weight)‐1. 3. Pressor doses of vasopressin of 100 pmol h‐1 (100 g body weight)‐1 and less did not significantly alter the clearance of p‐aminohippurate (PAH) in either conscious or anaesthetized rats. A dose of 1000 pmol h‐1 (100 g body weight)‐1 significantly decreased PAH clearance in both conscious and anaesthetized animals. 4. Inulin clearance was unchanged by non‐pressor doses of vasopressin in both conscious and anaesthetized rats. Moderately pressor doses decreased inulin clearance in conscious animals only. The highest dose administered (1000 pmol h‐1 (100 g body weight)‐1) decreased inulin clearance in both conscious and anaesthetized rats. 5. Pressor doses of vasopressin had a biphasic effect on the filtration fraction in conscious rats. The filtration fraction decreased with doses of vasopressin at the lower end of the pressor range but increased with the highest dose of 1000 pmol h‐1 (100 g body weight)‐1. In contrast the filtration fraction did not change significantly with moderate pressor doses in anaesthetized rats but was increased by doses of 100 and 1000 pmol h‐1 (100 g body weight)‐1. 6. It is concluded that pressor doses of vasopressin lower than 100 pmol h‐1 (100 g body weight)‐1 do not decrease renal plasma flow rate in conscious or pentobarbitone‐anaesthetized rats. The results suggest that the inconsistent effects of vasopressin on renal blood flow reported in the literature are due, at least in part, to the wide range of doses used.
Ionic channels and signal conduction in single remyelinating frog nerve fibres.
Authors: Shrager P
Published: December 2014

1. Ionic currents have been measured in single demyelinated and remyelinating frog sciatic nerve fibres by means of the loose patch clamp technique. Axons were demyelinated by a surgical intraneural injection of lysolecithin and recovery was followed for up to 5 months. 2. Removal of myelin debris continued for the first 2 weeks post‐injection. Proliferating Schwann cells were then seen within the lesion. As remyelination proceeded new nodes of Ranvier were formed in regions that previously were internodal. Original nodes, marking the transition from old to new myelin, could be identified at all stages. 3. Peak amplitudes of internodal transient inward Na+ currents were constant over the first 2 months and increased by about 60% after 5 months. Internodal currents in remyelinated axons were recorded after a second injection of lysolecithin to remove the thin myelin sheath. 4. Records from paranodal sites neighbouring transition nodes contained transient outward currents that were strongly voltage dependent and seemed to reflect activation of a very high density of Na+ channels just outside the patch. This sharp gradient in channel density at original nodes persisted throughout the period of remyelination studied suggesting that lateral diffusion from these sites is limited. These currents were never seen at internodal sites nor were they found at new nodes of Ranvier. 5. Paranodal inward current amplitudes in new nodes were similar to those in original (transition) nodes. 6. No transient inward Na+ currents were detected in Schwann cells adhering to demyelinated axons or free standing within the area of the lesion. 7. Conduction in single remyelinating fibres was studied by measuring membrane currents that flowed in response to an invading propagating action potential. At 2 weeks post‐injection, prior to the formation of myelin, conduction was decremental, but activation of internodal Na+ channels allowed signals to penetrate further into the demyelinated zone than would have been possible by passive spread alone. After an additional 3 weeks, following formation of thin myelin sheaths, conduction was significantly improved and the fractional activation of Na+ channels was increased. 8. The results suggest that Na+ channels at new nodes of Ranvier come neither from original nodes nor from Schwann cells. They may represent a moderate aggregation of existing internodal channels. New nodes seem to possess a gradient of Na+ channel density that is much less steep than that at original nodes. Continuous conduction appears to be limited to short (approximately 0.2 mm) lengths of demyelinated axons.(ABSTRACT TRUNCATED AT 400 WORDS)
Mechanism of release of calcium from sarcoplasmic reticulum of guinea‐pig cardiac cells.
Authors: Beuckelmann D J , Wier W G
Published: December 2014

1. The mechanisms that control release of Ca2+ from the sarcoplasmic reticulum (SR) of guinea‐pig ventricular cells were studied by observing intracellular calcium concentration ([Ca2+]i transients) and membrane currents in voltage‐clamped guinea‐pig ventricular myocytes perfused internally with Fura‐2. 2. Sarcolemmal Ca2+ current was identified through the use of tetrodotoxin (TTX) and Ca2+ channel antagonists (verapamil) and agonists (Bay K 8644). 3. Changes in [Ca2+]i attributable to release of Ca2+ from the SR were identified through the use of ryanodine, which abolishes the ability of the SR to release Ca2+. Ryanodine‐sensitive increases in [Ca2+]i could be elicited either by depolarization or by repolarization (from depolarizing pulses to relatively positive membrane potentials). 4. At appropriate voltages, it is the initial fast change in [Ca2+]i elicited by either depolarization or repolarization that is abolished by ryanodine, and is defined here as ryanodine sensitive. 5. The amplitude of the ryanodine‐sensitive [Ca2+]i transient elicited by depolarization had a bell‐shaped dependence on membrane potential with a maximum of about 500 nM at 10 mV, and with the upper minimum between 60 and 70 mV. Verapamil‐sensitive current activated over approximately the same potential range as the [Ca2+]i transient, with a peak amplitude at 10 mV, and a reversal potential of 65 mV. 6. When a holding potential of ‐68 mV and TTX (30 microM) were used, the most negative pulse potential at which activation of an inward current occurred was ‐49 mV while changes in [Ca2+]i occurred at ‐43 mV. 7. Ryanodine‐sensitive increases in [Ca2+]i elicited by repolarization (tail transients) were maximal for repolarization to 0 mV. Smaller changes in [Ca2+]i than maximal were elicited by repolarization to both more positive and more negative potentials than 0 mV. The peak amplitude of the verapamil‐sensitive tail currents elicited by repolarization increased continuously as the membrane was repolarized to potentials more negative than 60 mV. 8. Increasing depolarizing pulse duration beyond 10‐20 ms did not increase the amplitude of the [Ca2+]i transient, but prolonged it. 9. The experimental results are compared to the predictions of two theories on the mechanism of excitation‐contraction coupling: Ca2+‐induced release of Ca2+ (CICR), as it has been formulated from data in skinned cardiac cells, and a charge‐coupled release mechanism (CCRM), as it has been formulated to explain excitation‐contraction coupling in skeletal muscle. 10. Some of the results are clearly not consistent with certain features of a charge‐coupled release mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)
Maintained changes in motoneuronal excitability by short‐lasting synaptic inputs in the decerebrate cat.
Authors: Crone C , Hultborn H , Kiehn O , Mazieres L , Wigström H
Published: December 2014

1. During investigation of the tonic stretch reflex in the unanaesthetized decerebrate cat we observed that a short train of impulses in Ia afferents from the soleus muscle (or its synergists) may cause a prolonged activity in the soleus muscle as judged by EMG and tension recordings. This excitability increase, which outlasted the stimulus train, could stay virtually constant during long periods (even minutes), but could be terminated at any time by a train of impulses in, for example, the peroneal nerve. 2. Gradation of the strength of stimulation and the duration of the train of impulses show that the amount of maintained excitability increase depends‐within some limits‐on the total amount of Ia impulses. 3. In paralysed preparations a short train of impulses in Ia afferents from any part of the triceps surae, caused a maintained increase of the efferent activity in the nerves to triceps surae and a maintained increase of the triceps surae monosynaptic test reflex. These experiments demonstrate the existence of a central mechanism (in the spinal cord and/or the brain stem), which is responsible for the maintained excitability increase seen in motoneurones to the homonymous and synergic muscles. 4. In acute spinal preparations it was not possible to demonstrate any long‐lasting excitability increase by a train of Ia impulses. Following intravenous administration of the serotonin precursor 5‐hydroxytryptophan, mimicking the tonic activity of these pathways in the decerebrate state, it was again possible to elicit the long‐lasting excitability increase by a train of impulses in Ia afferents. A subsequent I.V. injection of methysergide (a serotonin receptor blocker) abolished the long‐lasting excitability increase. This set of experiments demonstrates that the basic mechanism responsible for the maintained excitability increase is located at segmental level, and involves serotonergic systems. 5. It was demonstrated that activation of several ipsilateral and crossed reflex pathways by trains of impulses in cutaneous or high‐threshold muscle afferents could trigger a maintained excitability increase of those motoneurone pools which were activated by the stimulation. Trains of stimuli to facilitatory regions in the brain stem could also cause a long‐lasting excitability increase of motoneurones. Furthermore, activation of all reflex pathways which mediate postsynaptic inhibition to a motor nucleus (including recurrent inhibition via Renshaw cells) could terminate the prolonged excitability increase of that particular motor nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)
Ionic mechanisms of adenosine actions in pacemaker cells from rabbit heart.
Authors: Belardinelli L , Giles W R , West A
Published: December 2014

1. Whole‐cell and patch clamp techniques have been applied to cells isolated from the rabbit sino‐atrial (S‐A) node to study the ionic mechanism(s) of adenosine‐induced slowing of cardiac pacemaker activity. 2. Viable spontaneously active cells were isolated from the central region of the S‐A node of the rabbit heart by an enzymatic dispersion procedure similar to that reported by Giles & van Ginneken (1985) and van Ginneken & Giles (1988). In these spontaneously beating cells application of adenosine caused a dose‐dependent slowing accompanied by a small hyperpolarization of the maximum diastolic potential. Relatively high doses of adenosine (greater than 20 microM) caused complete arrest, associated with a hyperpolarization of 12‐15 mV. 3. In corresponding whole‐cell voltage clamp experiments adenosine activated a time‐independent potassium current, IK(ADO), which at ‐50 mV is approximately 30 pA in normal Tyrode solution and 50 pA in high [K+]o (20 mM) Tyrode solution. This current is similar to the one identified previously in guinea‐pig atrium (Belardinelli & Isenberg, 1983a; Kurachi, Nakajima & Sugimoto, 1986). 4. Patch clamp recordings of the single‐channel events underlying IK(ADO) showed that they have a conductance of approximately 25.0 +/‐ 1.9 pS. The whole‐cell or macroscopic current, IK(ADO), and the adenosine‐induced single‐channel events exhibit strong inward‐going rectification. 5. Adenosine in doses (10 microM) which significantly activate IK(ADO) failed to produce any measurable effect on the calcium current, ICa, in these isolated cardiac pacemaker cells. However, after ICa has been enhanced by the addition of isoprenaline, adenosine (1‐10 microM) caused a significant inhibition: it reduced ICa back to approximately the control levels. 6. A similar ‘indirect’ effect of adenosine was observed on If, the slow time‐ and voltage‐dependent inward current which is activated by hyperpolarizing these S‐A node cells. Adenosine (10(‐5) M) failed to influence the control or basal If; however, after If was enhanced by isoprenaline, adenosine markedly inhibited it. 7. These results provide explanations for both the direct and the indirect effects of adenosine in mammalian cardiac pacemaker tissue: activation of IK(ADO), and of a time‐independent background potassium current and inhibition of ICa and If, respectively. Since it is known that there is significant adrenergic tone in the mammalian S‐A node both the indirect and the direct effects of adenosine may be of physiological importance.
Time‐resolved X‐ray diffraction studies on the effect of slow length changes on tetanized frog skeletal muscle.
Authors: Amemiya Y , Iwamoto H , Kobayashi T , Sugi H , Tanaka H , Wakabayashi K
Published: December 2014

1. The mechanism of the enhancement and the deficit of isometric force by slow length changes in frog skeletal muscle was studied with the time‐resolved X‐ray diffraction technique, using intense X‐rays of synchrotron radiation. 2. When a tetanized muscle was slowly stretched by 4% from sarcomere lengths 2.3‐2.4 microns, the force rose to a peak during stretch and then decreased to a steady level 10‐15% higher than that immediately before stretch. 3. The intensity of the 1,1 equatorial reflection decreased nearly linearly during stretch and then again increased after the completion of stretch, reaching a steady level 12 +/‐ 5% (mean +/‐ S.D., n = 11) lower than that immediately before stretch. The above 1,1 intensity change was roughly a mirror image of the force change. 4. The intensity of the 1,0 equatorial reflection showed no marked changes in response to a slow stretch, except for an initial transient increase observed occasionally. 5. If a tetanized muscle was slowly released by 4% from sarcomere lengths 2.3‐2.4 microns, the steady force attained after the completion of release was lower than that immediately before release. 6. The 1,1 intensity increased slightly during release, while the 1,0 intensity did not change significantly. 7. The half‐width of both the 1,0 and the 1,1 reflections did not change appreciably in response to slow length changes. 8. Slow length changes always produced changes in the spacing between the reflections as expected from the constant‐volume behaviour of the myofilament lattice. 9. These results indicate that a slow stretch produces disordering of the myofilament lattice in such a way that the thin filaments are displaced from trigonal positions in the thick filament lattice. The resulting increase in the overall repulsion forces between the filaments may lead to the enhanced isometric force after stretch.
Cardiovascular responses to stimulation of cardiac receptors in the cat and their modification by changes in respiration.
Authors: de Burgh Daly M , Kirkman E , Wood L M
Published: December 2014

1. In cats anaesthetized with a mixture of chloralose and urethane, stimulation of cardiac receptors by left atrial injections of veratridine had little or no effect on pulmonary ventilation but caused bradycardia, systemic hypotension and hindlimb vasodilation with a latency of 3.3 s. 2. The hindlimb vasodilatation was due largely, if not entirely, to a reduction in sympathetic vasoconstrictor activity. 3. Similar cardiovascular responses occurred when the arterial blood pressure was maintained constant and also in artificially ventilated animals. 4. When the cardiac receptors were excited during a period of apnoea which was induced reflexly by electrical stimulation of the central cut end of a superior laryngeal nerve, the cardio‐inhibitory response to left atrial injections of veratridine was enhanced but the size of the vasodilator response was unaffected. 5. In contrast, the cardiovascular effects of stimulation of the carotid body chemoreceptors, bradycardia and hindlimb vasoconstriction were enhanced by the laryngeal input. 6. The possible central mechanism responsible for the differential modulation of cardiac receptor and carotid chemoreceptor reflexes by respiration are discussed.
Activation of human muscles at short muscle lengths during maximal static efforts.
Authors: Gandevia S C , McKenzie D K
Published: December 2014

1. Human muscle endurance is apparently enhanced during maximal voluntary contractions at short muscle lengths (McKenzie & Gandevia, 1987) but the ability of subjects to activate muscles fully at short lengths has not been established. Therefore this study examined the voluntary capacity to activate muscles fully at control (near resting) lengths and at decreased muscle lengths. Changes in mechanical properties of twitch responses to electrical stimulation of relaxed muscles at short muscle lengths were also documented. The abductor digiti minimi, elbow flexors and tibialis anterior were studied in five subjects. 2. For the three muscle groups, the mean reduction in twitch force between the control and short muscle lengths ranged from 46‐51%. AT the short length there was a 9‐13% reduction in the contraction time and a 21‐27% reduction in the half‐relaxation time. Maximal voluntary force declined by 21‐49% at the short muscle length. A reduction in muscle length produced a shift to the right of the force‐frequency curve as determined by brief trains of electrical stimuli. 3. During maximal efforts single or brief trains of two to four supramaximal stimuli, delivered to the parent nerve or motor point, failed to increase the force at a latency appropriate for onset of a muscle twitch in some but not all attempts. Each subject achieved ‘maximal activation’ of the muscle in a similar proportion of attempts at the control and short muscle lengths. 4. These results suggest that maximal voluntary activation of motoneurone pools is possible at short muscle lengths and that the central nervous system is able to maintain the discharge of motoneurones close to ‘fusion’ frequency despite a decrease in the temporal characteristics of the isometric twitch.
The role of potassium channels in Schwann cell proliferation in Wallerian degeneration of explant rabbit sciatic nerves.
Authors: Chiu S Y , Wilson G F
Published: December 2014

1. Patch clamp studies of whole‐cell ionic currents and biochemical studies of proliferation were carried out on Schwann cells of myelinated axons in explant segments of sciatic nerves of adult rabbit maintained in culture for 0‐10 days. 2. Schwann cell proliferation, as assayed by [3H]thymidine incorporation and by electron microscopic autoradiography, showed an increase following nerve explant. Proliferation proceeded in parallel with a gradual hyperpolarization of the resting potential and an increase in K+ currents in Schwann cells of myelinated axons. 3. The relation between K+ channels and proliferation was studied by incubating explant nerves in the presence of various K+ channel blockers. Quinine, TEA and 4‐aminopyridine (4‐AP), which blocked K+ currents in Schwann cells, were found also to block Schwann cell proliferation in a dose‐dependent fashion and over similar concentrations. Electron microscopy showed that TEA did not retard myelin and axonal break‐down which is thought to be the source of mitogens for Schwann cell proliferation. 4. The relation between resting potential and proliferation was studied by incubating explant nerves in depolarizing culture media. Depolarizing monovalent cations (K+ and Rb+) led to a marked inhibition of Schwann cell proliferation. However, Cs+ and NH4+, which did not depolarize Schwann cells in patch clamp studies, also inhibited proliferation. Gramicidin and veratridine also inhibited proliferation. 5. The results suggest that the expression of K+ channels is functionally important for Schwann cell proliferation in Wallerian degeneration. A possible link between K+ channel and proliferation might be via a hyperpolarization of the resting membrane potential which occurs when Schwann cells proliferate.