bluuebunny/crossref_metadata_2025 huggingface dataset:
Receptive field organization and response properties of spinal neurones with axons ascending the dorsal columns in the cat.
Authors: Brown A G , Brown P B , Fyffe R E , Pubols L M
Published: December 2014

Micro‐electrode recordings were made from single post‐synaptic axons in the dorsal columns of cats anaesthetized with chloralose and paralysed with gallamine triethiodide. The recordings were made from the L5 segment and the axons were shown to project to the upper cervical level. Forty‐eight units were recorded and the axons had conduction velocities of 22‐61 ms‐1, averaging 38.3 ms‐1. Excitatory receptive fields were complex in many units, being made up of clearly defined, separate, low and high threshold areas. The receptive fields were often discontinuous. Only a few units behaved as if they received excitatory input from a single class of mechanoreceptors. A minority (13%) of units had labile, excitatory receptive fields that expanded in size during the recording period. About 40% of the units had inhibitory receptive fields. These were of two main types: either small and within or adjacent to the excitatory field, or large and separated from or adjacent to the excitatory field. The great majority of units had resting discharges upon isolation and these consisted of single impulses or bursts of impulses at short intervals separated by longer, irregular periods. The time course of inhibition produced by electrical stimulation of cutaneous nerves suggested presynaptic inhibitory components to the inhibition. Some inhibitory curves were very prolonged with maxima at about 100 ms and total durations of up to 400 ms. The complexity of the receptive field organization in these dorsal horn neurones is discussed, as is their possible significance as input neurones to the dorsal column nuclei.
Carotid baroreceptor reflex regulation of forearm vascular resistance in man.
Authors: Ebert T J
Published: December 2014

The carotid baroreflex regulation of forearm vascular resistance in man is uncertain. Forearm vascular resistance, blood pressure and R‐R interval responses to carotid sinus stimulation were therefore measured in seven healthy men. Carotid stimuli were delivered by gradually applying neck pressure, neck suction or neck suction during simultaneous low‐level lower‐body negative pressure. Mean arterial blood pressure and R‐R interval responses to neck suction and pressure were immediate and were sustained throughout the periods of stimulation. In contrast, forearm vascular responses, were transient. During simultaneous mild lower‐body negative pressure (which decreases cardiopulmonary baroreceptor stimulation and increases forearm vascular resistance), neck‐suction‐induced forearm vasodilation was exaggerated and sustained throughout the entire period of neck suction. There was a linear relationship between the level of resting forearm vascular resistance and the change in resistance produced by carotid stimuli. It is concluded that reflex changes in forearm vascular resistance provoked by carotid baroreceptor stimuli are immediate and evanescent in man. Simultaneous reduction of cardiopulmonary baroreceptor activity heightens the magnitude and duration of forearm vasodilation induced by carotid baroreceptor stimulation.
Extravagal innervation of canine tracheal stretch receptors.
Authors: Vidruk E H
Published: December 2014

In dogs an extravagal pathway consisting of the pararecurrent nerve, the ramus anastomoticus, the internal branch of the superior laryngeal nerve, and the superior laryngeal nerve carries nerve fibres from the upper trachea. A segment of the upper trachea innervated by fibres in this pathway was isolated in situ and ventilated separately from the rest of the respiratory tract. Single unit and whole nerve neurograms recorded from the pararecurrent nerve, the ramus anastomoticus, and the interior branch of the superior laryngeal nerve demonstrated discharge patterns characteristic of airway stretch receptors. The discharge was strongly modulated by ventilatory manoeuvres of the isolated tracheal segment but not the rest of the respiratory tract. The number of tracheal stretch receptors with fibres in this non‐vagal pathway was found to be similar to the number innervated by vagal pathways. A search for the presence of extravagal fibres innervating rapidly adapting receptors, however, was unsuccessful. A non‐vagal pathway exists between tracheal stretch receptors and the nodose ganglion. The functional significance of this pathway was not determined.
The effect of temperature on the nerve‐blocking action of benzyl alcohol on the squid giant axon.
Authors: Harper A A , Macdonald A G , Wann K T
Published: December 2014

The action of benzyl alcohol was studied on the voltage‐clamped giant axons of Loligo forbesi. The depressant effect of 7.5 mM‐benzyl alcohol on the action potential amplitude and peak rate of rise was more marked at a low (8 degrees C) than at a high temperature (16.5 degrees C). A small depolarization (approximately 5 mV) was also produced. These effects were usually reversible. Benzyl alcohol (7.5 mM) selectively depressed the amplitude of the peak early current. The maximum inward current was depressed to 0.65 and 0.67 of the control value at 20 degrees C and 7 degrees C respectively. This effect was usually reversible. Benzyl alcohol also depressed the peak inward conductance (gNa but had no effect on the time to peak early current. A small reversible decrease in the time constant of inactivation (tau h) was caused by benzyl alcohol (7.5 mM). This was usually reversible on washout of the anaesthetic. Benzyl alcohol (7.5 mM) had no effect on the time course of activation or the amplitude of the delayed outward current. The curve of the steady‐state inactivation parameter (h infinity) for the Na current against the conditioning membrane potential was shifted by benzyl alcohol in a hyperpolarizing direction (at h infinity = 0.5 the shift was an average of 3.3 mV and was reversible). Increasing the temperature from 7 to 20 degrees C shifted the curve in a depolarizing direction by approximately 10 mV. The reason for the increased nerve‐blocking action of benzyl alcohol at the lower temperature is discussed.
The relationship between hypoxic pulmonary vasoconstriction and arterial oxygen tension in the intact dog.
Authors: Orchard C H , Sanchez de Leon R , Sykes M K
Published: December 2014

The relationship between the magnitude of hypoxic pulmonary vasoconstriction (h.p.v.) and arterial oxygen tension (Pa,O2) has been studied in intact anaesthetized dogs. Radioactive 133Xe was infused continuously into the inferior vena cava. A tracheal divider made it possible to vary the inspired gas composition to each lung independently. With constant ventilation the 133Xe in the mixed expired gas from each lung was proportional to the blood flow to that lung. Unilateral ventilation of the left lung with 7% oxygen produced a diversion of blood flow away from the lung and a reduction in Pa,O2. Repeated hypoxic stimuli produced a progressively greater reduction in the blood flow to the hypoxic lung and a progressive increase in Pa,O2. Administration of a beta‐adrenergic agonist, dobutamine hydrochloride, during ventilation of the left lung with 7% oxygen, resulted in an increased blood flow to the left lung and a further decrease in Pa,O2. Addition of CO2 to the inspired gas resulted in an increased diversion of blood flow away from the hypoxic lung but a decrease in Pa,O2. Respiratory alkalosis induced by over‐ventilation decreased the hypoxic vasoconstriction and increased Pa,O2 slightly. However acid‐base changes induced by infusion of 1 N‐lactic acid or 8.4% NaHCO3 had no significant effects on the magnitude of the hypoxic vasoconstriction, or on Pa,O2, during hypoxic ventilation of the left lung. The magnitude of hypoxic vasoconstriction and Pa,O2 in the experiments described in 3, 4 and 5 above were positively correlated (r = 0.885), showing that the vasoconstriction may help to maintain Pa,O2. It is suggested that the effects of CO2 on h.p.v. and Pa,O2 may be explained largely by the changes in alveolar oxygen pressure (PA,O2) which are secondary to changes in PA,CO2.
Modulation by intracellular ATP and cyclic AMP of the slow inward current in isolated single ventricular cells of the guinea‐pig.
Authors: Irisawa H , Kokubun S
Published: December 2014

Effects of ATP and of cyclic AMP on membrane current systems were investigated in isolated single ventricular cells from guinea‐pig hearts by applying the suction electrode method. The intracellular milieu was dialysed with various solutions which were perfused continuously through the suction pipette. The presence of ATP, cyclic AMP and EGTA in the perfusion solution kept the plateau phase of the action potential almost intact for as long as 30 min. With depolarizing voltage‐clamp pulses from holding potentials between ‐30 and ‐40 mV, the slow inward current (isi) was activated at potentials positive to ‐20 mV. The inactivation time course of isi was fitted by two exponential components in the potential range between ‐10 mV and +30 mV. By increasing ATP from 2 to 9.5 mM in the solution, the amplitude of isi was increased and the slow component of inactivation was accelerated. The steady‐state current‐voltage relationship (I‐V curve), exhibited a negative slope that became steeper after increasing the ATP concentration. The current was shifted towards the outward direction between ‐40 mV and ‐10 mV and became more inward between ‐10 mV and +40 mV. Increase of the cyclic AMP concentration from 30 to 60 microM also enhanced the amplitude of isi, but the negative slope in the steady‐state I‐V curve was unaffected. Assuming that the concentration of free Ca2+ in the cell was well buffered at a low level by the EGTA‐Ca buffer solution in the pipette, it was concluded that [ATP]i and [cyclic AMP]i exert a direct influence on membrane current systems of the ventricular cell.
Calcium‐channel gating in frog skeletal muscle membrane: effect of temperature.
Authors: Cota G , Nicola Siri L , Stefani E
Published: December 2014

Voltage‐clamp experiments using the three micro‐electrode method were performed to study the temperature dependence of the calcium current ICa in intact twitch skeletal muscle fibres of the frog. Contraction was blocked by recording in hypertonic sucrose solutions. For depolarizations smaller than 0 mV the decay of the transient, slow, inward current, recorded in the presence of external tetraethylammonium (TEA+) and by replacing Cl‐ for CH3SO3‐, followed a complex time course. For larger depolarizations, after the initial inward current, there was a prominent, slow, outward current which showed two phases: after reaching a peak (time to peak 1.0 sec, peak amplitude 20‐50 microA/cm2 at 20 mV) it slowly declined to a steady level in about 2‐3 sec at 23 degrees C. The inward current was greatly reduced or abolished by the adding of 2 mM‐Cd2+ or by replacing external Ca2+ with Mg2+. The amplitude and time course of slow, outward currents were not obviously modified by replacing Ca2+ with Mg2+, having the two described phases. However, in the presence of Cd2+ the first transient phase of the outward current was not detected and only outward currents slowly increasing to a steady level were observed. Reliable ICa records were obtained by further blocking K+ outward currents by incubating the muscles in a K+‐free TEA+‐ and Cs+‐containing solution prior to experiments. Tubular space clamp was improved by recording ICa from small fibres with 20‐30 microns radius. The decay phase of ICa under a maintained depolarization in incubated muscles was fitted by a single exponential. The corresponding rate constant determined between 12 and 24 degrees C strongly depended on temperature, as expected for a gating process. The values for the activation energy and the corresponding Q10 (calculated for a 10‐20 degrees C transition) were respectively: 17.5 +/‐ 1.0 kcal/mole and 2.9 +/‐ 0.2 at 0 mV, and 18.0 +/‐ 1.5 kcal/mole and 3.0 +/‐ 0.3 at ‐20 mV. The activation phase of ICa, analysed following the m alpha h Hodgkin‐Huxley kinetic model, showed a similar temperature dependence with a Q10 of 3.0 +/‐ 0.3. The peak amplitude of ICa and the limiting Ca2+ permeability had a lower Q10 value of about 1.6. For a given temperature the rate constant of decay was independent of ICa peak amplitude in disagreement with a current‐dependent process (intratubular Ca2+ depletion or intracellular Ca2+ accumulation) for the decay of ICa. In conclusion, our results favour a gating process (inactivation) as the principal mechanism underlying the decay phase of ICa under a maintained depolarization.
The action of hydrocarbons and carbon tetrachloride on the sodium current of the squid giant axon.
Authors: Haydon D A , Urban B W
Published: December 2014

The effects of the n‐alkanes propane to hexane, cyclopropane, cyclopentane and cyclohexane and carbon tetrachloride on the ionic currents and electrical capacity of the squid giant axon membrane have been examined. Both the peak inward and steady‐state outward currents were reduced reversibly by each substance, though propane at 1 atm had very little effect. The membrane capacity at 100 kHz was reduced by all substances except propane at 1 atm. Na currents were recorded in intracellularly perfused axons before and during exposure to the hydrocarbons and the records were fitted with equations similar to those proposed by Hodgkin & Huxley (1952). Shifts in the curves of the steady‐state activation and inactivation parameters (m infinity and h infinity) against membrane potential, changes in the peak heights of the activation and inactivation time constants (tau m and tau h) and reductions in the maximum Na conductance (gNa) have been tabulated. The effects of the various hydrocarbons and carbon tetrachloride on the parameters of the Hodgkin‐Huxley equations suggest that the suppression of the Na current by these substances originates from several different phenomena. The underlying physico‐chemical events are considered in the light of the observed capacity changes and of information on artificial pore‐containing membranes.
The effects of catecholamines on pumping activity in isolated bovine mesenteric lymphatics.
Authors: McHale N G , Roddie I C
Published: December 2014

Bovine mesenteric lymphatics of 8 cm length were cannulated and arranged so that pressure changes produced by spontaneous contractions and accompanying flow could be measured. The mean frequency of spontaneous contractions, although constant for any one vessel, varied between vessels from 0.5 to 5.2 beats/min (mean 2.6, S.D. 1.6, n = 33). Noradrenaline (100 ng/ml.) invariably increased frequency of contractions but flow was increased only in those vessels which had a low resting frequency. In those vessels which had a higher resting frequency, flow was decreased despite the increase in frequency because stroke volume decreased. This may have been due to increased pace‐maker activity causing desynchronization of the contractile activity in the vessel wall and thus decreased effectiveness of pumping. High doses (greater than 1 microgram/ml.) of noradrenaline invariably depressed flow. Isoprenaline slowed the frequency of spontaneous contractions and this either had little effect on flow (due to an increased filling time and thus stroke volume) or depressed it, finally abolishing it entirely at higher doses. It is concluded that in suitable dosage (which varies for different vessels) noradrenaline is capable of enhancing flow and this might, at least in part, explain the increase in lymph flow resulting from noradrenaline infusion in living animals.
Actions of barium and rubidium on membrane currents in canine Purkinje fibres.
Authors: Cohen I S , Falk R T , Mulrine N K
Published: December 2014

The actions of Ba2+ and Rb+, two blockers of background K+ conductance, were investigated. Recent studies performed on ungulate Purkinje fibres have suggested that the pace‐maker current is an inward current activated by hyperpolarization. This hypothesis is based on the assumption that Ba2+ reduces the inwardly rectifying background K+ conductance without affecting the pace‐maker current. Addition of 5 mM‐BaCl2 to the bathing Tyrode solution decreases background K+ permeability and eliminates the reversal of the pace‐maker current. The reversal reappears on return to Ba2+‐free Tyrode solution. 5 mM‐BaCl2 also reduces the time‐dependent current at pace‐maker potentials positive to about ‐95 mV in 4 mM‐K+ Tyrode solution. The pace‐maker current in Ba2+ Tyrode solution usually does not have an exponential time course, and often decays non‐monotonically. It can take more than two minutes to reach a steady state. The fast initial component of membrane current, which is observed on hyperpolarizing in the pace‐maker potential range in Purkinje fibres and which has been called the ‘depletion current', is still present in Ba2+ Tyrode solution, but is reduced or eliminated if 10 mM‐CsCl is added to the Ba2+ Tyrode solution. The addition of Cs+ is accompanied by an outward shift in membrane current in Ba2+ Tyrode solution. Ba2+ reduces the background K+ permeability in a dose‐dependent manner. Addition of between 0.5 and 1 mM‐BaCl2 achieves a maximum effect. Raising the amount of BaCl2 above this level reduces the time‐dependent current even when no further effect on background permeability is observed. Rb+ substitution for K+ reduces the magnitude of the pace‐maker current at potentials positive to ‐100 mV, eliminates the reversal of the pace‐maker current, shifts the activation range to more negative potentials, and decreases the voltage dependence of pace‐maker current kinetics. Rb+ addition to Tyrode solution has little effect on pace‐maker current magnitude or time course positive to ‐90 mV, but does shift the reversal to more negative potentials. The available evidence suggests that the pace‐maker current in Ba2+ Tyrode solution is an inward current activated by hyperpolarization. However, Ba2+ blocks an unknown fraction of the pace‐maker current in a dose‐dependent, and possibly voltage‐dependent manner. Also, the presence of a slow component of pace‐maker decay suggests that the standard Hodgkin‐Huxley formalism for the analysis of pace‐maker currents is inappropriate.
The role of the septum in the control of the milk ejection reflex in the rat: effects of lesions and electrical stimulation.
Authors: Lebrun C J , Poulain D A , Theodosis D T
Published: December 2014

Experiments were undertaken to determine the role of the septum on the afferent control of the milk ejection reflex in lactating rats. Massive septal lesions were produced by passing radio‐frequency current through lesioning electrodes. Intramammary pressure recordings during suckling showed no significant alterations either in the frequency of milk ejections or in their amplitude and time course. Electrophysiological recordings of identified oxytocin‐secreting neurones in supraoptic nuclei of septal‐lesioned rats engaged in suckling showed that the pattern of background electrical activity and of the high frequency discharges at milk ejection were normal. The weight of litters from rats lesioned on the third day post‐partum increased in a way parallel to that of control litters up to the fifteenth post‐natal day. Electrical stimulation was applied bilaterally to the lateral septum in trains of long duration (20‐55 min) at varying frequencies. Frequencies of 5 and 10 Hz interrupted the reflex during the period of stimulation. At 1 Hz, milk ejections were not interrupted but the intervals between successive milk ejections were significantly increased in comparison to the intervals before stimulation. Electrical stimulation applied to the septum in short trains of 1 or 3 min at 5 and 10 Hz significantly delayed the appearance of the subsequent milk ejection. At 1 Hz, no effect was observed. Septal stimulation at 1 Hz for 20 min or more did not significantly alter the electrocorticogram during the period of stimulation. Stimulation at 5 Hz for the same period of time always desynchronized the e.e.g. for several minutes after the cessation of stimulation. It is concluded that the septum is not essential for the onset and the maintenance of reflex milk ejections during lactation. The results suggest, however, that in the normal non‐anaesthetized animal, septal activation could modulate the frequency of milk ejections.
Latency of pancreatic fluid secretory response to intestinal stimulants in the dog.
Authors: Singer M V
Published: December 2014

The effect of atropine and truncal vagotomy on the latency of the secretory response of the exocrine pancreas to rapid intraduodenal injection of L‐tryptophan, sodium oleate and HCl or to rapid intraportal injection of secretin or CCK octapeptide has been determined in conscious dogs with pancreatic fistulae. The intraduodenal stimulants were injected either alone or in the presence of an intravenous infusion of secretin, CCK octapeptide or a combination of both hormones. The mean latency of response to tryptophan alone (62 +/‐ 2 s), oleate alone (64 +/‐ 5 s) and HCl alone (91 +/‐ 3 s) was significantly longer (P less than 0.05) than the latency to intraportal secretin (28 +/‐ 5 s) or CCK octapeptide (45 +/‐ 4 s). Infusion of secretin alone or with CCK octapeptide significantly shortened the latency of response to tryptophan (38 +/‐ 3 s) and oleate (41 +/‐ 5 s), but had no effect on the latency to intraduodenal HCl (96 +/‐ 4 s). Atropine and truncal vagotomy both increased the latency to intraduodenal tryptophan and oleate threefold but did not affect the latency to intraduodenal HCl or intraportal secretin or CCK octapeptide. These data support the hypothesis that the stimulus to pancreatic fluid secretion evoked by intraduodenal HCl is humoral rather than neural, while the responses to intraduodenal tryptophan and oleate are mediated, at least in part, via an enteropancreatic, vago‐vagal, cholinergic reflex.
Intracellular calcium concentration during hypoxia and metabolic inhibition in mammalian ventricular muscle.
Authors: Allen D G , Orchard C H
Published: December 2014

Papillary muscles from rats, cats and ferrets were microinjected with aequorin, a photoprotein which emits light as a function of Ca2+ concentration. The effects of hypoxia and different types of metabolic inhibition on intracellular Ca2+ concentration ([ Ca2+]i) and tension were studied. 2. Exposure of the muscle to hypoxia (PO2 less than 5 mmHg) or CN‐ caused a reversible decrease in developed tension, with no change in the magnitude of the Ca transient associated with each contraction. The rate of decline of the Ca transient was decreased slightly but significantly during these interventions. 3. In half the preparations examined, the initial fall in tension produced by hypoxia was interrupted by a short‐lived increase in developed tension. No change in the Ca transient was associated with this increase in tension. 4. After exposure of papillary muscles to glucose‐free Tyrode solution for short periods (less than 1 hr), hypoxia and CN‐ had a similar effect on the magnitude of the light transient and developed tension to section 2 above. After perfusion with glucose‐free Tyrode solution for longer periods (greater than 2 hr), hypoxia and CN‐ caused a greater decrease in developed tension and a marked decrease in the magnitude of the Ca transient. 5. The addition of CN‐ to papillary muscles which were superfused with Tyrode solution containing 2‐deoxyglucose instead of glucose, caused a rapid decrease in the magnitude of the Ca transient and of developed tension. These changes were not fully reversible. 6. In muscles which developed an hypoxic contracture, the resting [Ca2+]i did not rise by more than a factor of 1.4. 7. It is concluded that when glycolysis can proceed, inhibition of oxidative phosphorylation results in a decrease in developed tension with no change in the magnitude of the Ca transient. This decrease in the apparent sensitivity of the contractile proteins to Ca2+ is attributable to the decrease in intracellular pH known to occur in this situation. There may also be a second mechanism tending to reduce the Ca transient under these conditions. 8. During inhibition of glycolysis and oxidative phosphorylation, developed tension falls as a result of decreased Ca transients. This could be because the free energy of hydrolysis of ATP falls below the level required to pump Ca from the myoplasm to the sarcoplasmic reticulum.
Repetitive doublets in human flexor carpi radialis muscle.
Authors: Bawa P , Calancie B
Published: December 2014

Single‐motor‐unit activity was recorded from flexor carpi radialis of two human subjects. 2. A large number of units showed repetitive doublets at the onset of slow recruitment. A unit starting with doublets would transfer to a normal firing pattern as the force increased. 3. At different speeds of ramp contractions, the number of doublets discharging at the onset of contraction decreased as the speed of contraction increased. 4. Both low‐ and high‐threshold units discharged repetitive doublets. Motor units which could discharge doublets showed higher maximal firing rates than those units which did not fire doublets. 5. Short interspike intervals were also observed at the onset of ballistic movements. From the comparison of these short interspike intervals and the short intradoublet intervals we suggest that the two arise from two distinct phenomena in the spinal cord. 6. Linked potentials were observed both with single spikes and doublets. Their origin may lie in the spinal cord or the muscle unit itself or both.
The effects of deafferentation and spinal cord transection on synapse elimination in developing rat muscles.
Authors: Caldwell J H , Ridge R M
Published: December 2014

The proportion of muscle fibres innervated by more than one motoneurone (polyneuronal innervation) was measured in the fourth deep lumbrical muscle of young rats following either unilateral deafferentation or spinal cord isolation (cord transection combined with bilateral deafferentation). 2. Unilateral deafferentation at 7 days of age did not affect the subsequent time course of synapse elimination in the developing muscle. 3. Spinal cord isolation at 7 days led to a prolongation of the time course of synapse elimination in the muscle, levels of polyneuronal innervation approaching zero beyond about 30 days (about 20 days in normal animals). The raised levels of polyneuronal innervation in these animals were not associated with significant terminal sprouting at end‐plates, but were associated with multiple axonal inputs to end‐plates as is found in younger normal animals. This was shown by zinc iodide and osmium staining. Also some muscle fibres had two and sometimes three separate end‐plates. 4. Spinal cord isolation in rats 19 or more days old resulted in a reappearance of multiple innervation. This was largely due to ultraterminal sprouting. 5. It is concluded that unilateral deafferentation alone causes no change in the time course of synapse elimination. The multiple innervation caused by total deafferentation and spinal transection is attributed to the lack of activity of these muscles.
Slow changes in currents through sodium channels in frog muscle membrane.
Authors: Almers W , Stanfield P R , Stühmer W
Published: December 2014

We used a patch clamp to measure Na currents across 10‐15 micron diameter circular patches of frog and rat skeletal muscle membrane. We tested for electrophoretic mobility of Na channels, by applying steady lateral fields (of the order of 10 mV micron‐1) across the wall of the patch pipette. Application of steady negative potentials to the inside of the pipette resulted in a fall in the number of functional Na channels in the patch. This fall took several minutes to complete and was reversible. It was assayed by applying suitable depolarizations at approximately 11 sec intervals. When a steady lateral field was applied in the absence of changes in membrane potential of the patch, the loss of Na current was virtually abolished. Thus it was not due to electrophoretic movement of channels, but instead to depolarization of the sarcolemma. Evidently, a very slow inactivation of Na conductance operates in skeletal muscle. In frog muscle, the rate constants for loss and recovery of Na current were about 0.1 min‐1 (17 degrees C) at resting potential. Rate constants were higher at more positive and at more negative membrane potentials. Current amplitude was reduced to 0.5 at about ‐76 mV. Roughly similar results were found in rat omohyoid muscle. A further inactivation mechanism, whose rate was intermediate between conventional fast inactivation and the very slow process described here, was present also in both rat and frog muscle. In frog muscle, lateral fields do not alter the potential dependence of fast inactivation. Either the surface charge due to membrane lipids does not influence inactivation or the lipids immediately surrounding the Na channel are restricted in their mobility.
Influence of pH on capillary filtration coefficient of rat mesenteries perfused with solutions containing albumin.
Authors: Gamble J
Published: December 2014

A preparation of rat mesentery was vascularly isolated from the intestine and perfused with a physiological salt solution containing either Ficoll 70 or bovine serum albumin, to act as colloidal agents. The capillary filtration coefficient (Kf; units, ml. min‐1 100 g‐1 mmHg‐1) was measured by following the weight change after graded increases in venous pressure. At pH values greater than 7.05, Kf, during perfusion with 3 and 4% bovine serum albumin solutions, was 0.219 +/‐ 0.023 (mean +/‐ S.E. of mean), ninety‐eight observations in thirteen experiments, which was significantly less than the value of 0.507 +/‐ 0.038 which was obtained during perfusion with albumin solutions at pH less than 7.05, seventy‐six observations in eleven experiments, (P less than 0.05). The value of Kf obtained during perfusion with 4% Ficoll solutions was 0.267 +/‐ 0.018, 119 observations in sixteen experiments, and remained uninfluenced by pH over the same range that had been used with the albumin solutions; however, perfusion of the tissues with Ficoll solutions at pH greater than 7.05, after perfusion with albumin solution pH less than 7.05, did cause the Ficoll‐derived value of Kf to rise to 0.502 +/‐ 0.055, seventy‐two observations in eleven experiments. It was concluded that the changes in Kf were not due to pH alone, but were mediated by albumin at acidic pH.
Developmental changes in the distribution of acetylcholine receptors in the myotomes of Xenopus laevis.
Authors: Chow I , Cohen M W
Published: December 2014

The acquisition and distribution of nerve fibres and of acetylcholine (ACh) receptors were examined in the myotomes of Xenopus laevis during normal development. This muscle is well‐suited for investigating temporal relationships during neuromuscular synaptogenesis because the age of the Xenopus embryo at the onset of innervation can be assessed with an accuracy of about one hour. Myotomal nerve fibres were visualized after staining them with nitroblue tetrazolium and ACh receptors were examined after exposure to alpha‐bungarotoxin labelled with 125I or fluorescent dye. Nerve fibres were seen in the myotomes of some embryos as early as stage 19 (20 . 75 hr) and in virtually all embryos by stage 24 (26 . 25 hr). From the outset they were located mainly at the ends of the myotomes, but some myotomes also exhibited nerve fibres in more central regions. ACh receptors were already present in myotomes by stage 19 (20 . 75 hr) and initially had a widespread, uniform distribution. The density of extrajunctional ACh receptors increased until stage 36 (50 hr) and then declined less than 3‐fold over the next 10 days of development. Discrete patches of high ACh receptor density began to appear at the ends of the myotomes at stage 22 (24 hr) and were seen in almost all embryos by stage 26 (29 . 5 hr). ACh receptor patches were also seen in central regions of some myotomes and these were usually aligned in patterns which resembled the course of nerve fibres. The present findings suggest that myotomal muscle cells in Xenopus embryos begin to acquire ACh receptors shortly before the arrival of nerve fibres and that discrete patches of ACh receptors begin to form at presumptive synaptic sites on the average about 3 hr after the arrival of the nerve fibres. The latter delay is considerably shorter than that in developing rat muscle. The temporal and spatial relationships between nerve fibres and the development of ACh receptor patches in Xenopus myotomes in vivo are consistent with findings in Xenopus cell cultures which indicate that nerve fibres can rapidly induce ACh receptor localization at sites of nerve‐‐muscle contact.
Local and systemic effects of tetrodotoxin on the formation and elimination of synapses in reinnervated adult rat muscle
Authors: Taxt Torfinn
Published: December 2014

1. Polyneuronal innervation of normal and reinnervated fourth deep lumbrical muscle fibres was studied with tension measurements and intracellular recordings. From the tenth day after a complete crush of the muscle nerve, some of the reinnervated muscles were completely paralysed for up to 15 days by local application of tetrodotoxin (TTX) to the sciatic nerve. Other animals received only systemic infusion of TTX during the muscle reinnervation.

2. Measurements of tetanic‐tension overlap suggested that about 6% of the muscle fibres in the normal lumbrical muscle were polyneuronally innervated, while intracellular recordings suggested that the percentage was as high as 25%. This discrepancy was mainly due to the presence of one small, sub‐threshold end‐plate potential (e.p.p.) and one large, suprathreshold e.p.p. in almost all polyneuronally innervated muscle fibres.

3. Intracellular recordings during muscle reinnervation showed that the extent of polyneuronal innervation reached a maximum of 50% 10‐15 days after denervation and that by 16‐20 days this had decreased to a level similar to that found in normal muscle.

4. After a week of total muscle paralysis the extent of polyneuronal innervation had increased to about 80%, estimated by both tension measurements and intracellular recordings. Subsequently, there was no sign of any net elimination of the polyneuronal innervation, even in muscles paralysed for up to two weeks. Many of the polyneuronally innervated fibres were innervated by at least two motor axons. each producing suprathreshold e.p.p.s.

5. In muscles contralateral to the paralysed muscles, the extent of polyneuronal innervation reached a maximum of 50% 10‐15 days after denervation as in reinnervated muscles not exposed to TTX. But in contrast to the subsequent decrease in the extent of polyneuronal innervation in animals which received no TTX, this level of polyneuronal innervation persisted in muscles contralateral to the paralysed muscles. The same was true for reinnervated muscles in animals which only received TTX systemically.

6. The increased level of polyneuronal innervation after TTX application was not caused by differences in the number of motor units or in number of muscle fibres.

7. Paralysed muscles relaxed much more slowly than non‐paralysed muscles at the end of a fused tetanic contraction. The tetanus/twitch ratio of these muscles was also smaller than in contralateral control muscles and the rise time of the twitch was greater.

8. It is concluded that a substantial fraction of the fibres in the normal lumbrical muscle of young rats is polyneuronally innervated. After reinnervation, the normal innervation pattern is re‐established, but no net elimination of the polyneuronal innervation occurs unless either nerve or muscle or both are active. A net elimination of synapses is also prevented when TTX is present systemically in low concentrations.
Paralysis of frog skeletal muscle fibres by the calcium antagonist D‐600.
Authors: Eisenberg R S , McCarthy R T , Milton R L
Published: December 2014

The Ca2+ channel blocker D‐600 (methoxyverapamil) paralyses single muscle fibres of the frog: fibres exposed to the drug at 7 degrees C give a single K+ contracture after which they are paralysed, unable to contract in response to electrical stimulation or further applications of K+. Paralysed fibres contract in response to caffeine and have normal resting potentials and action potentials. Fibres treated with D‐600 at 22 degrees C are not paralysed. Paralysed fibres warmed to 22 degrees C recover contractile properties: they twitch and give K+ contractures. Other workers have shown that D‐600 blocks a Ca2+ channel at room temperature; thus, the paralytic action of D‐600 is probably mediated by a different membrane protein, perhaps a different Ca2+ channel from that blocked at room temperature. These results suggest that the binding of D‐600 can disrupt the mechanism coupling electrical potential changes across the T membrane to Ca2+ release from the sarcoplasmic reticulum.
Vasoactive intestinal polypeptide: a putative transmitter in the canine gastric muscularis mucosa.
Authors: Angel F , Go V L , Schmalz P F , Szurszewski J H
Published: December 2014

The nature of the inhibitory transmitter in the canine gastric muscularis mucosae was studied in vitro using superfusion techniques. The inhibitory effect of nerve stimulation (10 V, 200 mus, 10 Hz) was not altered by adrenergic, cholinergic or serotonergic antagonists. Adenosine triphosphate had no effect on spontaneous mechanical activity. Nucleotide pyrophosphatase and apamin had no effect on the response to nerve stimulation. Alpha‐chymotrypsin abolished the inhibitory effect of nerve stimulation. Radioimmunoassay of the muscle indicated the presence of gastrin/cholecystokinin‐substance P‐ and vasoactive intestinal polypeptide (VIP)‐like immunoreactivity. Of the three peptides present, only VIP produced a concentration‐dependent relaxation. A substance with VIP‐like immunoreactivity was released during nerve‐induced relaxation of the muscle, and its release was blocked by tetrodotoxin and calcium‐depleted solution. The inhibitory effect of nerve stimulation was abolished by VIP antiserum. These data strongly support the hypothesis that VIP or a closely related peptide is an inhibitory neurotransmitter in the canine gastric muscularis mucosae.
Sodium and chloride co‐transport by preimplantation rabbit blastocysts.
Authors: Benos D J , Biggers J D
Published: December 2014

Influxes of Na+ and Cl‐ across the trophectodermal epithelium of 6 day post coitum (p.c.) rabbit blastocysts are partially interrelated. This relationship was investigated under conditions in which either the external [Na+] or [Cl‐] concentration was varied. Our results indicate that an ouabain‐insensitive, furosemide‐sensitive, Na+:Cl‐ co‐transport system exists in the 6 and 6.5 day p.c. rabbit embryo, but not in the 5 day p.c. blastocyst. There was no dependence of NaCl uptake on the presence of K+ in the bathing medium. No evidence of Na+/H+ or Cl‐/HCO3‐ exchange systems in the rabbit blastocyst was found. The effects of furosemide, exogenous cyclic AMP, and various exogenous prostaglandins on Na+ and Cl‐ movements were studied. Cyclic AMP and/or prostaglandin E1 may regulate the operation of this Na+:Cl‐ co‐transport system.
Bradykinin‐induced contractions of bovine mesenteric lymphatics.
Authors: Azuma T , Ohhashi T , Roddie I C
Published: December 2014

The mode of action of bradykinin (BK) on bovine mesenteric lymphatics was investigated by recording isometric tensions and action potentials in the isolated longitudinal segments. Addition of BK in concentrations from 10(‐10) to 4 X 10(‐6) M caused dose‐related tonic contractions. BK in a low concentration accelerated the rhythm of action potential discharges in the spontaneously beating preparations and elicited frequent discharges of action potentials and a rapid rise in smooth muscle tone associated with phasic contractions. BK in high concentrations (more than 10(‐7) M) caused a further rise of tension in the preparations which had already been depolarized in a high‐K solution. The contraction induced by 4 X 10(‐9) M‐BK in the standard solution was abolished in a Ca‐free environment or in the presence of a Ca‐antagonist, 10(‐4) M‐D‐600, though more than 50% of the contraction caused by 10(‐6) M‐BK still remained in both circumstances. In a Ca‐free solution containing 1 mM‐EGTA (Ca‐free standard solution), 10(‐6) M‐BK caused a slight contraction even after high‐K‐induced contractions were completely blocked. The contractile response to 10(‐6) M‐BK in the Ca‐free standard solution was augmented after activation of beta‐receptors. It is concluded that the BK‐induced contractions may be closely related to an increased Ca influx through the membrane and release of membrane‐bound and intracellular Ca. The increased uptake of Ca into the BK‐sensitive intracellular store may contribute to the relaxing effect of beta‐agonist.
Central and proprioceptive influences on the activity of levator costae motoneurones in the cat.
Authors: Hilaire G G , Nicholls J G , Sears T A
Published: December 2014

The role of central respiratory drive, muscle spindles and tendon organs in producing respiratory movements has been studied in the cat by recording from motoneurones supplying a set of small axial muscles inserted between each rib and the vertebra immediately rostral, the levatores costae. The levator costae muscles are active during normal inspiration but activity is progressively stronger in the muscles located in more caudal thoracic segments. Intracellular recordings from levator costae motoneurons show a characteristic central respiratory drive potential (c.r.d.p.), comprising phases of depolarization during inspiration alternating with expiratory phased hyperpolarization due to post‐synaptic inhibition. Loading or unloading the levator costae muscles increases and decreases, respectively, their normal inspiratory activity. Electrophysiological and histological analysis of levator costae afferents reveals that each muscle contains three to five spindles and two to three tendon organs. By dissecting the levator costae nerve, afferent discharges from muscle spindle primary and secondary endings and those from tendon organs were recorded ‘in continuity’ and used to trigger an averager for analysing the synaptic potentials they evoke in levator costae motoneurones. Monosynaptic excitation and oligosynaptic inhibition originate from spindle (primary and secondary endings) and from tendon organ afferents respectively. Peculiarly a monosynaptic excitation has been evoked from a tendon organ. The action of the levator costae muscle on the respiratory movements of the ribs in the different thoracic spaces was analysed in relation to their anatomical properties and to the activity of the other respiratory muscles. The levator costae muscles, because of their relatively small size and well‐defined population of proprioceptors, appear to provide a favourable preparation for studying the integrative action of the motoneurone.
On the mechanism of contraction and desensitization induced by substance P in the intestinal muscle of the guinea‐pig.
Authors: Holzer P , Petsche U
Published: December 2014

The contractile effect of substance P on the longitudinal muscle of the isolated guinea‐pig small intestine and the desensitization of the muscle which occurs on prolonged exposure to the peptide have been investigated. All experiments were performed in the presence of atropine. The response to a substance P concentration which produced a nearly maximal effect was not sustained but faded rapidly. It was found that not elimination of substance P from the bath, but desensitization of the muscle to substance P was the main cause for the fading of contraction. Desensitization of the muscle to substance P only developed if the muscle was exposed to the peptide for a certain time. The degree of and the time needed for recovery from desensitization were directly related to concentration of substance P and contact time. Tetraethylammonium (3 mM), which reduces the membrane conductance for K+, enhanced the potency of substance P in contracting the muscle and reduced the fading of contraction. Noradrenaline (295 nM), which increases the K+ conductance, produced opposite effects. Lowering the extracellular Ca2+ concentration to one‐tenth decreased the potency of substance P in contracting the muscle, accelerated the fading of contraction, and reduced the ability of the muscle to respond to a second addition of substance P after the response to the first addition had faded away. Concentrations of substance P (22 nM) and tetraethylammonium (30 mM), which produced nearly maximal contractions, slightly enhanced the efflux of 86Rb from pre‐loaded muscle strips. Both substances, however, caused a sustained reduction of 86Rb efflux from strips depolarized by high [K+], the effect of substance P being smaller than that of tetraethylammonium. The effect of substance P and tetraethylammonium on 86Rb efflux appeared independent of the extracellular [Ca2+]. On exposure of the muscle to substance P (22 nM) for 8 min the intracellular uptake of 45Ca was first decreased and then increased while the 45Ca influx was instantly enhanced by tetraethylammonium (30 mM) or K+ (108 mM). The delayed increase in 45Ca influx caused by substance P was also observed in muscle strips depolarized with high [K+].(ABSTRACT TRUNCATED AT 400 WORDS)
A pace‐maker‐like current in the sheep atrium and its modulation by catecholamines.
Authors: Earm Y E , Shimoni Y , Spindler A J
Published: December 2014

A modified single‐sucrose‐gap system was used to study sheep atrial trabeculae under voltage‐clamp conditions. A time‐ and voltage‐dependent current system is described, which resembles the current if in Purkinje fibres. This current was activated at membrane potentials of between ‐60 and ‐70 mV in many fibres. The addition of Ba2+ reduced the instantaneous current (the ‘jump') and thus facilitated the study of the current if. Current tails were more prominent in the presence of TTX and Mn2+. Most experiments were done in the presence of Ba2+, Mn2+ and TTX. Standard envelope tests and conductance measurements indicated that this current is an inward current, activated on hyperpolarization. We have also labelled the atrial current if. The instantaneous fully activated current‐voltage relationship, i(E) was found to be linear in the activation range. Increasing the level of K+, which increased the current magnitude, also increased the slope of the i(E) curve. The current magnitude was also dependent on the level of Na+ in the medium. The current magnitude was increased by adrenaline or isoprenaline. Only a small part of the increase could be attributed to a shift in the voltage dependence of the gating kinetics. The shifts in activation curves were much smaller (3‐4 mV in the depolarizing direction) than those in Purkinje fibres. Large shifts in activation curves were obtained with theophylline, indicating that the presence of Ba2+ or Mn2+ did not occlude any shifts by adrenaline. The magnitude of if was increased by theophylline, with a further increase by adrenaline. There is therefore no mutual occlusion of the two effects on if. The slope of the i(E) curve was increased by isoprenaline, indicating that there was an increase in conductance. The presence of propranolol did not prevent the increase in current amplitude by isoprenaline. A direct effect of catecholamines on the channel is suggested.