bluuebunny/crossref_metadata_2025 huggingface dataset:
Osmoreceptors or sodium receptors: an investigation into ADH release in the rhesus monkey.
Authors: Swaminathan S
Published: December 2014

1. ADH secretion was studied in trained, preoperated conscious monkeys undergoing water diuresis after administration of isosmolar hypertonic solutions of different substances into any one of the following sites: (i) anterior third ventricle, (ii) the hypothalamus, just anterior to the third ventricle and (iii) common carotid artery. 2. Free water clearance was continuously monitored and the ADH released was measured by bio‐assay on the same animals after administering graded doses of standard arginine vasopressin in a comparable manner. 3. Intraventricular infusions of hypertonic solutions of NaCl or Na acetate released significant amounts of ADH while sucrose or mannitol of comparable osmolality were ineffective. Graded increases in the concentration of NaCl infused into the c.s.f. resulted in secretion of ADH proportional to log Na concentration. 4. Infusion of the same hypertonic solutions into the anterior hypothalamus released ADH, though Na salts were more effective than the sugars. 5. Hypertonic solutions of NaCl, Na acetate, sucrose or mannitol were effective in releasing ADH when injected via the carotid artery, but hypertonic solutions of NaCl were significantly more effective than the other solutions. 6. These findings may be explained by the hypothesis that the ‘osmoreceptors’ of Verney are Na sensitive receptors composed of dendrites innervating the specialized ependyma of the anterior part of the third ventricle.
The effects of 5‐hydroxytryptamine, histamine and acetylcholine on the reactivity of the lung of the anaesthetized dog.
Authors: Dixon M , Jackson D M , Richards I M
Published: December 2014

1. Anaesthetized dogs were given aerosols of 5‐hydroxytryptamine (5‐HT), histamine and acetylcholine; the effects on the changes in total lung resistance (RL) and dynamic lung compliance (Cdyn) produced by electrical stimulation of the peripheral cervical vagi, and I.V. histamine and acetylcholine were studied. 2. Pretreatment with 5‐HT significantly potentiated the increases in RL caused by vagal stimulation, histamine or acetylcholine. Pretreatment with histamine significantly potentiated the increases in RL caused by vagal stimulation but the potentiation of the increases in RL produced by histamine and acetylcholine were not significant. Pretreatment with acetylcholine did not potentiate the increases in RL due to vagal stimulation, histamine or acetylcholine. The falls in Cdyn produced by vagal stimulation, histamine or acetylcholine were not potentiated by pretreatment with aerosols of 5‐HT, histamine or acetylcholine. 3. The effects of I.V. histamine, 5‐HT and acetylcholine on RL and Cdyn were studied when given alone and when combined with vagal stimulation. 4. Vagal stimulation significantly potentiated the increases in RL due to 5‐HT and histamine, but did not affect the increases in RL caused by acetylcholine or the falls in Cdyn produced by any of the three agonists. 5. By comparing these results with those from a previous study, it is concluded that, for the three agents studied, in order for increased irritant receptor discharge to reflexly increase RL, the agent has to increase the reactivity of the airway to vagal stimulation. It is also concluded that the degree of vagally mediated broncho‐constriction can be varied by changing either the afferent limb through a change in irritant receptor discharge, or the efferent limb, by a change in airway reactivity.
The conductance of sodium channels under conditions of reduced current at the node of Ranvier.
Authors: Sigworth F J
Published: December 2014

1. The single sodium channel conductance gamma and the number of channels N were estimated from fluctuation analysis in voltage‐clamped nodes of Ranvier under conditions that decreased the size of the sodium current. 2. Reduction of the sodium current by depolarizing prepulses had no effect on gamma, and, in cases where it could be determined, had no significant effect on N. Partial block of the sodium conductance with tetrodotoxin and saxitoxin also did not affect gamma significantly, but reduced N. 3. gamma was reduced to about 40% of the control value at ‐5 mV when the pH of the external solution was reduced to 5.0. The pH dependence of gamma is consistent with the theories of Woodhull and of Drouin & Neumcke. 4. The differing effects of prepulses, toxins and pH are interpreted in view of the different time scales of channel inactivation or block under these conditions. 5. The nearly unchanged gamma with prepulses and partial toxin block provides further evidence for the absence of interactions among sodium channels.
Chromaffin cell action potentials and their possible role in adrenaline secretion from rat adrenal medulla.
Authors: Kidokoro Y , Ritchie A K
Published: December 2014

1. The role of action potentials in adrenaline secretion was investigated in the rat adrenal medulla. The effects of various treatments on adrenaline secretion from the perfused adrenal medulla were compared with the effects of similar treatments on spike frequency in dissociated adrenal chromaffin cells. 2. KCl concentrations between 10 and 20 mM increased the extracellularly recorded spike frequency of dissociated adrenal chromaffin cells. Upon perfusion by a KCl concentration of 30 mM there was an initial brief burst of spikes followed by a period of inactivity in the continued presence of 30 mM‐Kcl. Tetrodotoxin (TTX, 6 microM) decreased the amplitude and frequency of the KCl evoked spikes. 3. The rate of adrenaline secretion from the isolated perfused rat adrenal gland increased as the KCl concentration was raised to 10 and up to 120 mM. Secretion which was evoked by KCl concentrations between 10 and 20 mM was partially inhibited by TTX. At KCl concentrations of 30 mM or greater evoked secretion was no longer affected by TTX. 4. CoCl2 (5 mM) blocked KCl increase of spike frequency and also blocked stimulation of adrenaline secretion by all concentrations of KCl tested. 5. Tetraethylammonium chloride (10 mM), which decreased spike frequency but greatly prolonged the spike duration, enhanced secretion induced by 15 mM‐Kcl. 6. The results are consistent with the following interpretation. The TTX insensitive portion of the KCl stimulated adrenaline secretion is due to Ca influx through voltage dependent Ca channels which are open as a consequence of the steady‐state level of KCl depolarization. The TTX sensitive portion of secretion is indicative of an extra increment of Ca influx during spike activity enhanced by KCl. This increment of Ca influx may occur through voltage dependent Ca channels whose activation is facilitated by the voltage changes caused during the TTX sensitive Na component of the spike and possibly through the Na channel itself. 7. Stimulation of secretion by acetylcholine (ACh) in the perfused adrenal medulla was half maximal at 15 microM and began to saturate around 50 microM. Release was partially inhibited by TTX only when the concentration of ACh was 10 microM or less. The possible role of action potentials in ACh stimulated adrenaline release is discussed.
Functional capacities of tactile afferent fibres in neonatal kittens
Authors: Ferrington D. G. , Rowe Mark J.
Published: December 2014

1. Responses were recorded from individual tactile afferent fibres isolated by microdissection from the median nerve of pentobarbitone‐anaesthetized neonatal kittens (1‐5 days post‐natal age). Experiments were also conducted on adult cats to permit precise comparisons between neonatal and adult fibres.

2. Neonatal fibres with receptive fields on the glabrous skin of the foot pads were classified into two broad groups, a slowly adapting class (40%) which responded throughout a 1 sec period of steady indentation and a rapidly adapting or dynamically sensitive class comprising 60% of units. Fibres in these two groups had overlapping conduction velocities in the range 4·3 to 7·5 m/sec and were believed to be the developing Group II afferents of the adult.

3. Neonatal slowly adapting fibres qualitatively resembled their adult counter‐parts. They displayed graded stimulus‐response relations which, over the steepest segment of the curves, had mean slopes of 15·7 impulses/100 μm of indentation. Plateau levels of response were often reached at amplitudes of skin indentation of < 0·5‐0·7 mm.

4. Dynamically sensitive fibres with receptive fields on the glabrous skin were studied using sinusoidal cutaneous vibration which in the adult enables them to be divided into two distinct classes. However, in the neonate, they formed a continuum whether criteria of sensitivity or responsiveness were used.

5. In response to vibration neonatal fibres differed from adult ones according to the following quantitative indices: (i) sensitivity as measured by both absolute thresholds and thresholds for a 1: 1 pattern of response, both of which were higher in the neonate than in the adult at all frequencies > 50 Hz and differed by an order of magnitude at frequencies ≥ 200 Hz; (ii) responsiveness based on the mean impulse rate evoked at a fixed amplitude of cutaneous vibration; (iii) band width of vibratory sensitivity which in the neonate was confined to approximately 5‐300 Hz whereas in the two classes of adult units it covered the range 5‐800 Hz; (iv) capacity for coding information about vibration frequency. Impulse activity of neonatal fibres was less tightly phase‐locked to the vibratory stimulus and showed a poorer reflection of the periodic nature of the vibratory stimulus than impulse patterns of adult units.

6. The results reveal that tactile receptors and afferent fibres in the neonate are functionally immature. Their restricted coding capacities suggest that peripheral tactile sensory mechanisms impose limits on the ability of the new‐born animal to derive information about its tactile environment.
Intrinsic regulation of functional blood flow and water absorption in canine colon.
Authors: Granger D N , Kvietys P R , Mailman D , Richardson P D
Published: December 2014

1. Autoregulation of total and absorptive site blood flow and H2O fluxes were studied in canine colon during arterial pressure decreases and venous pressure elevations. 2. Reductions in arterial pressure caused proportional decreases in total colonic blood flow indicating no autoregulatory ability. In contrast, absorptive site blood flow was constant over an arterial pressure range of 40‐140 mmHg but decreased sharply below 40 mmHg. 3. Venous pressure elevation decreased total blood flow and increased resistance but had no effect on absorptive site blood flow over a range of 0‐30 mmHg. 4. Net H2O absorption was unchanged by alteration of arterial or venous pressure but the unidirectional H2O fluxes decreased with arterial pressure reduction and were unchanged by venous pressure elevation. 5. Adenosine infusion increased total and absorptive site blood flow and the unidirectional H2O fluxes yet had no effect on net H2O flux. 6. It was concluded that absorptive site blood flow is very well autoregulated in the colon but total blood flow is not. Net H2O absorption is maintained during decreased blood flow by maintenance of blood flow to the mucosa and by decreasing the back flux of H2O across the mucosa.
Feto‐maternal histoincompatibility and placental blood flow.
Authors: Auerbach R , Hay J B , Kubai L
Published: December 2014

1. We have designed experiments aimed at resolving some of the controversy concerning the effect of histoincompatibility on the development of the fetus and its placenta. 2. Experiments included the generation of pregnancies in which H‐2 compatible and H‐2 histoincompatible embryos were simultaneously present. Genetic markers (Brachyury and Kink) were used to facilitate determination of the H‐2 haplotype. Additional strain combinations were used to analyse the role of non‐H‐2 differences. 3. In addition to determining fetal and placental weights, blood flow to the placenta was measured by use of radioisotope‐labelled microspheres introduced into the arterial circulation. 4. Under the conditions of our experiments we have failed to detect differences in fetal weight, in placental weight, or in placental blood flow. 5. Thus we support the increasingly prevalent view that histo‐incompatibility does not necessarily lead to changes in placental or fetal weight, and we add the additional finding that placental blood flow also is not significantly altered as a result of feto‐maternal incompatibility.
Effects of pregnancy on glucose handling by rat kidneys.
Authors: Bishop J H , Green R
Published: December 2014

1. Glomerular filtration rate (g.f.r.), and renal reabsorption and excretion of glucose, sodium and potassium were measured in 7‐8 day pregnant rats and age‐matched (12‐13 week old) virgin controls undergoing saline and glucose infusions. 2. Pregnancy was associated with an increased g.f.r. and a decreased urine flow rate during both infusions. 3. During saline infusion, more glucose was excreted in pregnant animals than in virgins but with no significant difference in fractional reabsorption. During glucose infusion, pregnant animals excreted less glucose than virgins, owing to a decrease in the filtered load but with no significant difference in fractional reabsorption. 4. During both saline and glucose infusion, pregnant animals excreted less sodium than virgin controls. 5. During saline infusion, pregnant animals excreted more potassium. During glucose infusion, pregnant animals excreted less potassium than control animals.
Effects of changing external potassium and chloride concentrations on the photoresponses of Bufo bufo rods.
Authors: Capovilla M , Cervetto L , Torre V
Published: December 2014

1. Intracellular responses to light were recorded from Bufo bufo rods in different ionic media. 2. The exposure of the retina to high external [K+] depolarized the rod and modified the time course of the photoresponse. The prominent initial transient of rod responses to bright flashes was drastically reduced in 5 mM‐external [K+] and completely disappeared in 26 mM. In high external [K+] the kinetics of responses to dim flashes were considerably slower than in control conditions. 3. When external [Cl‐] was changed from 120.6 to 10.6 mM the resting membrane potential decreased and the size of photoresponses increased. Changes in the kinetics similar to those described in high external [K+] were also observed. 4. In many cases exposure of the retina to low external [Cl‐] induced oscillations of the resting membrane potential that sometimes became sustained. This instability of the membrane completely disappeared upon restoring to normal conditions. 5. The present results may be explained by assuming the existence of a voltage‐ and time‐dependent conductance active near the dark level of membrane potential. This hypothesis can be represented by an equivalent electrical circuit that includes an inductance (Detwiler, Hodgkin & McNaughton, 1980).
Characteristics of voltage‐dependent conductance in the membranes of a non‐excitable tissue: the amphibian lens.
Authors: Delamere N A , Duncan G , Paterson C A
Published: December 2014

1. The electrical conductance of the frog lens membranes was observed to increase when the lens was depolarized by current, and to decrease when the lens was hyperpolarized. 2. The total lens conductance (GT) could be described by a voltage‐dependent component (GH) together with a voltage‐insensitive component (GO). 3. Conductance measured at the resting potential increased from 9.7 to 14.4 x 10(‐5) S when the lens was depolarized by 9.1 mV in 10(‐4) M‐ouabain. The increase of conductance could be explained by an increase of GH which resulted from the depolarization alone. 4. Potassium‐rich solutions influenced the conductance by increasing GH as the result of depolarization and by decreasing (blocking) GO. Small increases in the external potassium concentration (from 2.5 to 5 mM), which did not depolarize the lens, resulted in a decrease in resting conductance due to the blockade of GO. 5. Conductance‐voltage relationships established in 2.5 (control), 5, 12.5 and 25 mM external potassium could each be fitted to a single mathematical model by assuming that GO had been reduced for 5.0 (control) to 4.5, 3 and 1 x 10(‐5) S respectively by those increased potassium concentrations. 6. Barium (2 mM) depolarized the lens by 14.3 mV and decreased the resting conductance by 39%. When the lens was depolarized by a step current pulse in the presence of barium, the conductance increased with time after the onset of the current. Hyperpolarization elicited less time dependence of the conductance. 7. Barium reduced the extent to which lens conductance was dependent on voltage.
Factors affecting the supply of glucose to the heart of the rat, in vivo.
Authors: Daniel P M , Love E R , Pratt O E
Published: December 2014

1. The influx of glucose into the heart of intact, living, anaesthetized rats was measured when the levels of insulin the blood were (a) low (as a result of fasting), (b) normal, and (c) high (as a result of injecting insulin). The findings showed that the transport of glucose into cardiac cells is carrier‐mediated and is strongly insulin‐independent. 2. The major barrier to the supply glucose to the heart from the circulating blood is at the surface membrane of the cardiac cells, rather than at the endothelium of the cardiac capillaries. 3. The extracellular space of the heart was measured and was found to be approximately 25% of the cardiac tissue. 4. During life, glucose, as well as its analogue, 3‐O‐methylglucose passes across the membranes of the cells of the heart by means of a transport system which is strongly dependent upon insulin and appears to be carried‐mediated. A likely explanation for the effect of insulin is that it increases considerably the affinity of the transport carrier for glucose. Saturation of the carrier takes place when the levels of insulin and of glucose in the blood are high. However, when the concentration of insulin is low, e.g. during a fast, the affinity of the carrier for glucose is reduced so that saturation cannot be demonstrated. 5. It is suggested that the low level of insulin that is found in the blood in the early morning, which is due to the night fast, may lead to the cardiac dysfunction which often develops at that time.
The relationship between maximal ventilation, breathing pattern and mechanical limitation of ventilation.
Authors: Jensen J I , Lyager S , Pedersen O F
Published: December 2014

1. The extent to which the pattern of breathing at maximal ventilation in man is affected by the mechanical properties of the respiratory pump has been studied. 2. The maximal effort flow volume (MEFV) loop has been used to calculate the shortest possible inspiratory (TI) and expiratory (TE) durations associated with the highest ventilation for all tidal volumes (VT). These minimal TIS and TES hve been plotted on a VT‐TI‐TE diagram. 3. Such predicted minimal TIS and TES were compared with observed minimal values from five healthy subjects who tried to reach their maximal ventilations during three experimental conditions: maximal voluntary hyperventilation, rebreathing, and graded exercise. 4. We have found that exercise increases the maximal flows at all lung volumes and confirmed that rebreathing has no such effect. 5. During hyperventilation the mechanical limits were followed closely for all VTS. During exercise and rebreathing the VT‐TI and the VT‐TE relationships showed a definite maximum of VT at submaximal ventilation in half the cases. The calculated minimal TIS and TES were approached but not reached. This indicates that maximal ventilation is not entirely limited by the mechanical properties of the respiratory pump, but that mechanical factors influence the regulation of breathing pattern when ventilation approaches the maximal capacity of the respiratory pump.
Prolonged exposure to acetylcholine: noise analysis and channel inactivation in cat tenuissimus muscle.
Authors: Wray D
Published: December 2014

1. Micro‐electrodes were used to record membrane potential and associated noise at the end‐plate region of cat tenuissimus muscle (37 degrees C), during applications of acetylcholine (ACh) in continuously flowing Krebs solution containing eserine and tetrodotoxin. 2. Densensitization was assessed from the frequency of channel opening calculated from the noise variance. 3. At higher concentrations of ACh (10‐50 microM), desensitization occurred with an exponential fall to a plateau. 4. At low concentrations of ACh (1‐2 microM) only slight desensitization occurred and at a much lower rate. Frequency of channel opening decreased at the rate of 0.045 +/‐ 0.024 min‐1. Maximum frequency was (33 +/‐ 9) X 10(7)/sec while maximum depolarization was 20.5 +/‐ 1.4 mV (n = 11 cats). Depolarization was well maintained. 5. This slow rate of desensitization at low concentrations of ACh was confirmed in experiments where voltage clamped current, its associated noise, and miniature end‐plate current amplitude were measured. 6. At low concentrations of ACh (1‐2 microM) in the presence of eserine there was sustained block in neuromuscular transmission when twitch tension was measured. 8. It is concluded that the mechanism of neuromuscular block by ACh at around 1 microM concentration is by depolarization itself, not desensitization.
The calcium and frequency dependence of the slow inward current ‘staircase’ in frog atrium.
Authors: Noble S , Shimoni Y
Published: December 2014

1. Changes in the magnitude of the slow inward current in the frog atrium were monitored at different stimulation frequencies, using a double sucrose‐gap technique. 2. After short rest periods (1.5‐3.0 min), repetitive clamp depolarizations applied at frequencies ranging from 0.33 to 1 Hz (20‐60/min) resulted in a progressive increase in the slow inward current towards a new level. Action‐potential amplitudes and plateau levels usually showed similar increases under these conditions. 3. Changes in the magnitude of the slow inward current were also found when the frequency was changed during constant stimulation. 4. Replacement of calcium ions by strontium or barium ions led to an augmentation or reduction, respectively, of the ‘staircase’ effect, relative to the effect in calcium‐containing solutions. Barium ions were found to greatly increase the slow inward channel ‘recovery’ time. 5. The results suggest that calcium influx into amphibian atrial fibres contributes to the regulation of the slow inward conductance mechanism. Progressively increasing currents may underlie positive tension staircases.
Calcium inward current and related charge movements in the membrane of snail neurones.
Authors: Kostyuk P G , Krishtal O A , Pidoplichko V I
Published: December 2014

1. Isolated and intracellularly perfused neurones from the snail Helix pomatia have been investigated under voltage‐clamp conditions. Calcium inward current and asymmetric displacement current were examined. 2. Two components of the asymmetric displacement current have been distinguished. One of them was irreversibly blocked by intracellular fluoride together with the calcium inward current. Another component (about 20%) was not affected. The relation of the fluoride‐sensitive asymmetric displacement current to the activity of calcium channels was investigated. 3. The amounts of charge displaced by the on‐ and off‐responses of the asymmetric current were similar. The maximum charge displacement was between 1500 and 2000 electron charges/micrometers 2. 4. The normalized steady‐state voltage distribution curve of the displaced charge coincided with the square root of the normalized calcium conductance. The slope was 4 mV per e‐fold change for the calcium conductance and 8 mV for te charge distribution. Thus, the effective valencies were close to 6 (for the calcium conductance) and 3 (for the charge distribution), suggesting two gating particles per calcium channel. 5. The on‐process of the calcium inward current fitted m2 kinetics. The time constant tau m corresponded to the time constant tau ason of the asymmetric current in a wide range of tested voltages. This correspondence failed only at small depolarizations where tau m exceeded tau ason. 6. The ‘off’ time constants of the calcium inward current (tau Caoff) and the asymmetric current (tau asoff) examined at ‐40 mV did not depend significantly on the test pulse height. The ratio tau asoff/tau Caoff varied between 1.7 and 2.5. 7. Calcium inward‐current relaxation kinetics were measured for small shifts of membrane potential (Vtest = ‐2 mV) applied at the peaks of the current. The time constants were smaller than tau m and depended only weakly on voltage. 8. It is concluded that the fluoride‐sensitive asymmetric displacement current is related to the activation of calcium channels.
Effects of dynamic and static neck suction on muscle nerve sympathetic activity, heart rate and blood pressure in man.
Authors: Båth E , Lindblad L E , Wallin B G
Published: December 2014

1. Recordings of vasoconstrictor sympathetic activity in peroneal muscle fascicles, blood pressure, and heart rate were made in twelve subjects while stimulating carotid sinus receptors by continuous or sinusoidal (cycle durations 7.5, 15 and 30 sec) neck suction. Neural activity, quantified by counting the number of pulse synchronous sympathetic bursts (burst incidence), was correlated to the pressure sensed by carotid sinus receptors (= calculated diastolic transmural carotid pressure) and to pressure sensed by arterial baroreceptors not located in the neck (= diastolic blood pressure). 2. Sinusoidal neck suction induced rhythmical modulation of sympathetic activity which became less noticeable with increasing modulation of sympathetic activity which became less noticeable with increasing cycle duration. Static suction led to a non‐significant reduction of sympathetic burst incidence. 3. With sinusoidal stimuli the amplitude of the transmural carotid pressure variations were maximal at a cycle duration of 7.5 sec and decreased successively at cycles of 15 and 30 sec. Amplitudes of induces variations in R‐R intervals in the e.c.g. changed in a similar way but in contrast induced variations in diastolic blood pressure were minimal at a cycle duration of 7.5 sec and maximal at 15 sec. It is suggested that the main rate limiting factors for the blood pressure responses is the sluggishness of the peripheral vascular beds. 4. Sinusoidal neck suction always prolonged mean R‐R interval. This stimulus increased mean burst incidence in subjects with few bursts at rest and decreased burst incidence in subjects with many bursts at rest. These changes of burst incidence were linearly related to the increases of R‐R intervals. The findings demonstrate interindividual differences in balance between cardiac and peripheral vasoconstrictor responses to changes of baroreceptor activity. 5. It is concluded that fast changes in carotid sinus pressure effectively modulate sympathetic outflow to the muscles and thereby contribute to transient compensatory blood pressure responses. Static blood pressure control, on the other hand, probably depends more on baroreceptor control over the effector organs.
Two kinds of recurrent inhibition of cat spinal alpha‐motoneurones as differentiated pharmacologically.
Authors: Cullheim S , Kellerth J O
Published: December 2014

1. The effects of i.v. administration of the glycine‐antagonist strychnine nitrate and the GABA‐antagonists bicuculline hydrochloride and picrotoxin on the recurrent inhibition of lumbosacral alpha‐motoneurones were studied in cats anaesthetized with pentobarbitone sodium. 2. As revealed from both monosynaptic reflex experiments and intracellular recordings, each of the drugs generally reduced, but rarely abolished, the recurrent inhibition. The amount of reduction was more or less identical for bicuculline and picrotoxin. 3. By applying de‐ and hyperpolarizing currents intracellularly it could be shown that both the strychnine‐resistant and bicuculline/picrotoxin‐resistant recurrent inhibitory potentials were genuinely post‐synaptic in nature. 4. The strychnine‐resistant part of the recurrent inhibition had a later maximum and a longer duration than the part which was resistant to bicuculline/picrotoxin. 5. The time course of the strychnine‐resistant recurrent inhibition was more or less identical to that of the bicuculline/picrotoxin‐sensitive recurrent inhibition. 6. The bicuculline/picrotoxin‐resistant recurrent inhibition was blocked by strychnine and, vice versa, the strychnine‐resistant recurrent inhibition was blocked by bicuculline/picrotoxin. The combined administration of strychnine and bicuculline/picrotoxin always resulted in a virtual abolition of the recurrent inhibitory effects. 7. The values for central delay suggested that both the strychnine‐resistant and bicuculline/picrotoxin‐resistant inhibitions were mediated via disynaptic pathways. 8. The results suggest that both glycine and GABA act as transmitter substances of Renshaw cells in mediating recurrent inhibition to alpha‐motoneurones. 9. No organizational pattern of the two types of recurrent inhibition based on motor pool category or motor unit type could be detected.
Channel gating at frog neuromuscular junctions formed by different cholinergic neurones.
Authors: Breitschmid P , Brenner H R
Published: December 2014

1. Drug‐induced membrane current fluctuations were analysed at frog ectopic neuromuscular junctions formed de novo by somatic motoneurones and by preganglionic autonomic neurones of the vagus nerve, and at denervated end‐plates reinnervated by the vagus nerve. 2. At ectopic motor end‐plates, the mean open time of the ion channels activated by ACh is tau ACh = 1.8 +/‐ 0.1 msec (S.E.) at ‐70 to ‐90 mV and 15‐18 degrees C. Carbachol‐ and suberyldicholine‐induced channels have average open times tau Carb = 1.0 +/‐ 0.1 msec (‐80 mV, 6‐8 degrees C) and tau Sub = 3.3 +/‐ 0.1 msec (‐80 mV, 16‐18 degrees C). 3. The conductances gamma of single channels induced by ACh, carbachol and suberyldicholine are: gamma ACh = 21.0 +/‐ 1.1 pS (+/‐ S.E.), gamma Carb = 14.6 +/‐ 1.2 pS and gamma Sub = 22.1 +/‐ 1.2 pS. 4. The mean open times tau of the channels is prolonged as the membrane is hyperpolarized. Their voltage dependence is similar to that of normal end‐plate channels. 5. The average open time of ACh‐induced channels at ectopic vagus junctions is tau = 1.6 +/‐ 0.2 msec (S.E.) at ‐70 to ‐80 mV and 14‐15 degrees C. At denervated motor end‐plates reinnervated by vagal neurones, the mean channel open time is tau = 1.5 +/‐ 0.1 msec at ‐80 mV and 14‐18 degrees C. 6. At all vagus junctions, the synaptic currents are blocked by alpha‐bungarotoxin. 7. Somatic motoneurons and vagal neurones induce junctional folds in the muscle membrane where they contact it to form an ectopic end‐plate. Staining the ACh receptors of the motor end‐plates with horseradish peroxidase‐alpha‐bungarotoxin conjugate shows that the receptors are restricted to the junctional region of the muscle fibre membrane.
Effect of a ‘sickling pulse’ on calcium and potassium transport in sickle cell trait red cells
Authors: Bookchin Robert M. , Lew Virgilio L.
Published: December 2014

1. To trace the early development of the extensive functional membrane abnormalities found in sickle cell anaemia red cells which result from polymerization of haemoglobin S, we followed the effects on Ca and K transport of an in vitro sickling pulse in sickle cell trait (SA) red cells, whose membranes are initially normal.

2. Sickling induced a progressively larger uptake of Ca in fed, starved and ATP‐depleted SA cells, always substantially higher than that in normal (AA) red cells under comparable conditions. The fraction of ionized Ca within the SA cells, estimated from the equilibrium distribution of 45Ca induced by the ionophore A23187 was about 0·4 of the total Ca content and similar in SA and AA cells.

3. With ATP‐depleted SA cells, Ca uptake (representing Ca permeability) was maximal during sickling and was only partially reduced towards normal after desickling. Net Ca uptake during sickling of fed or starved SA cells reverted to net Ca loss upon reoxygenation, irrespective of the Ca gradient, indicating full restoration of the low Ca permeability of the control conditions.

4. Following desickling of both fed and starved SA cells, the rates of uphill extrusion of Ca gained during sickling were much smaller than those expected with normal Ca pumps operating at similar internal Ca concentrations.

5. After 2 hr sickling ATP levels in starved SA cells were reduced by 50% regardless of the presence or absence of Ca in the medium; therefore sickling‐induced Ca uptake was associated with no measurable consumption of ATP due to Ca‐pump activity.

6. With ATP‐depleted SA cells, a Ca uptake of 2‐3 μmole/l. cells elicited a maximal response of the K permeability system resulting in full equilibration of the K pools in the cell suspensions. Sickling of fed and starved SA cells produced a small increase in K permeability which was entirely independent of the presence or absence of Ca.

7. Sickled forms persisted after reoxygenation only with ATP‐depleted SA cells and were more frequent after sickling in the presence of Ca (about 20%) than in a Ca‐free medium (about 4%).

8. These findings show that initial sickling produces an increased Ca permeability whose extent and reversibility depends on the metabolic state of the cells, and a partial Ca‐pump failure, which appears to be irreversible. We confirm a small sickling‐related, reversible increase in K permeability but a Ca‐dependent increase in K permeability does not occur unless the cells are fully depleted of ATP. The implications for sequential development of related abnormalities in SS cells are discussed.
parallel secretion of secretory proteins and calcium by the rat parotid gland.
Authors: Kanagasuntheram P , Lim S C
Published: December 2014

1. The secretion of amylase, deoxyribonuclease, ribonuclease, protein and Ca2+ by the rat parotid gland in vitro was studied. 2. Isoproterenol and carbamoylcholine elicited a parallel discharge of amylase, deoxyribonuclease, ribonuclease and protein over a 40 min time period. 3. The composition of the secretion was independent of the secretogogue used for stimulation. When gland slices from the same animal were stimulated with isoproterenol, adrenaline, phenylephrine or carbamoylcholine, secretory enzymes and protein were secreted in constant proportions. 4. 45Ca injected intraperitoneally 16 h before stimulation with either isoproterenol or carbamoylcholine was released in parallel with amylase and protein. 5. The relative proportions of amylase, ribonuclease, deoxyribonuclease, protein and Ca present in isolated parotid gland secretory granules was identical to that of isoproterenol stimulated gland secretion. 6. It is concluded that the secretory proteins and Ca2+ are discharged in constant proportions by the rat parotid gland regardless of the mode of stimulation or the rate of secretion. The similarity in the composition of gland secretion and granule contents also suggests that enzymes and Ca2+ are released by exocytosis and not by diffusion across the apical plasma membrane.
Developmental changes in subthreshold pace‐maker currents in chick embryonic heart cells.
Authors: Clay J R , Shrier A
Published: December 2014

1. Small re‐aggregates of cells dissociated from the ventricles of 12‐or 17‐day‐old chick embryonic hearts have beating properties in low potassium tissue culture medium which differ from re‐aggregates prepared from 7‐day‐old hearts; 12‐day preparations either beat with a slower rate than comparable‐size 7‐day preparations or they are quiescent; 17‐day preparations usually do not beat. 2. A two‐micro‐electrode voltage‐clamp technique was used to analyse the membrane currents in these preparations in the ‐120 to ‐40 mV potential range. 3. A potassium ion membrane current was measured in 12‐day and 17‐day preparations which was qualitatively similar to the potassium ion current measured in 7‐day preparations (Clay & Shrier, 1981). It differed in that its amplitude was diminished in the ratio 1:0.2:0.03 over the 7‐, 12‐ and 17‐day sequence. Furthermore, its maximum time constant was 2 sec at both 12 and 17 days, as compared to 1 sec at 7 days, and its membrane potential range of activation was ‐80 to ‐70 mV at 12 and 17 days, as compared to ‐90 to ‐60 mV at 7 days. 4. The background current also changed with development, becoming less inward over the 7‐, 12‐ and 17‐day sequence. The voltage dependence of this change suggested that it was caused by a developmental decrease of the background sodium current. 5. The change in the background component is primarily responsible for the loss of automaticity over the 7‐, 12‐, and 17‐day sequence.
Dynamic properties of the inferior rectus, extensor digitorum longus, diaphragm and soleus muscles of the mouse.
Authors: Luff A R
Published: December 2014

1. Isometric responses to direct stimulation of inferior rectus (IR), extensor digitorum longus (EDL) and soleus (SOL) muscles and strips of diaphragm (DIA) muscle of the mouse were obtained. 2. The IR, EDL and DIA were qualitatively ‘fast‐twitch’, while the SOL was ‘slow‐twitch’. The isometric twitch contraction time was for IR, 3.7 ms; EDL, 6.9 ms; DIA, 13.2 ms; SOL, 20.9 ms (at 35 degrees C). Twitch: tetanus ratio for IR was unusually small (0.12) whereas that of DIA was unusually large (0.31). 3. The force‐velocity properties of the muscles were determined and the sarcomere speed of shortening calculated. The intrinsic speeds of shortening of EDL and IR were not significantly different from each other, and were 49.5 and 51.6 micrometers . s‐1 respectively; the value for SOL was 23.1 micrometers . s‐1 and the DIA was intermediate at 39.7 micrometers . s‐1. 4. The time course of the isometric twitch of the IR was about half that of the EDL whereas the force‐velocity properties of these two muscles were almost identical. This is very similar to the situation in the rat. 5. Some of the dynamic properties of the DIA were clearly intermediate between the typical ‘fast‐twitch’ EDL and IR and the typical ‘slow‐twitch’ SOL. This does not agree with the available histochemical evidence which suggests that the mouse diaphragm is a ‘fast‐twitch red’ muscle.
Interaction between perfusion pressure and sympathetic nerves in renin release by carotid baroreflex in conscious dogs.
Authors: Gross R , Hackenberg H M , Hackenthal E , Kirchheim H
Published: December 2014

1. The effect of bilateral carotid occlusion on carotid sinus pressure, systemic blood pressure, heart rate, renal blood flow, renal‐venous and arterial plasma renin activity was studied in twelve trained conscious foxhounds on a normal sodium diet (4.7 mmol/kg per day). 2. When renal perfusion pressure was allowed to rise with systemic pressure by 51.0 +/‐ 6.3 mmHg during carotid occlusion, renin release decreased by 72.3 +/‐ 22.2 ng/min (78% of control; P less than 0.05) while renal blood flow remained at its resting level of 232.7 +/‐ 20.1 ml/min (n = 8 dogs). 3. When renal perfusion pressure was maintained constant at 93.0 +/‐ 3.6 mmHg during carotid occlusion (suprarenal aortic cuff), renin release increased by 154.6 +/‐ 60.4 ng/min (73% of control; P less than 0.05), again there was no significant change of renal blood flow (n = 7 dogs). 4. After beta‐adrenergic blockade carotid occlusion increased systemic blood pressure by 47.7 +/‐ 7.8 mmHg, decreased renin release by 34.6 +/‐ 9.9 ng/min (67% of control; P less than 0.05) and had no effect on renal blood flow (n = 4 dogs). 5. When renal perfusion pressure was controlled at its resting level, no significant change of renin release and renal blood flow was observed during carotid occlusion in the surgically denervated kidney (n = 3 dogs) or in the intact kidney after beta‐adrenergic blockade (n = 4 dogs). 6. It is concluded that a reduction of carotid sinus pressure in the conscious dog increases renin release by a direct beta‐adrenergic stimulation without exerting vasomotor effects provided renal perfusion pressure is maintained at control level. The vascular receptor mechanism can effectively counteract the stimulating influence of the renal sympathetic nerves when perfusion pressure is allowed to rise.
Studies on secretion of catecholamines evoked by acetylcholine or transmural stimulation of the rat adrenal gland.
Authors: Wakade A R
Published: December 2014

1. A method of studying the secretion of catecholamines (CA) in the isolated perfused rat adrenal gland by transmural stimulation or by application of acetylcholine (ACh) has been described. 2. Secretion of CA was practically linear in response to ACh administration, starting from 4.42 microM to 1.32 mM. Transmural stimulation enhanced secretion from a stimulation frequency of 0.5‐‐3 Hz; the effect levelled at 10 Hz, and declined as frequency was raised to 30 Hz. The secretory response to transmural stimulation was maximal over 1 msec duration and 60 V. 3. Secretion evoked by transmural stimulation was blocked (70‐95%) by 0.31 microM‐tetrodotoxin (TTX) irrespective of stimulus duration, voltage and frequency of stimulation. Secretion evoked by ACh was depressed 43% by TTX. After mecamylamine (0.59 mM) treatment, secretory response evoked by either procedure was blocked by about 80%. 4. Adenosine (0.18 mM), adenosine monophosphate (0.28 mM), or adenosine triphosphate (0.19 mM) lowered CA secretion evoked by transmural stimulation by about 40%, but had no effect on secretion induced by ACh. 5. Isoprenaline (4.52 microM), propranolol (11.58 microM), clonidine (13.00 microM), phenoxybenzamine (3.30 microM), and 4‐aminopyridine (3 mM) did not modify CA secretion evoked by transmural stimulation or by ACh. 6. Perfusion of the adrenal gland with 0.25 mM‐Ca‐Krebs solution completely abolished CA secretion evoked by transmural stimulation, but ACh‐induced secretion was still 30‐50% of the control value. 20 mM‐Mg blocked electrically induced secretion by 60%, but that evoked by ACh was unaffected. 7. Perfusion with Ca‐free Krebs solution for 2 hr did not completely abolish the response. However, treatment with EGTA (5 mM) for 30 min totally blocked ACh‐induced secretion. 8. La or Mn were more effective in blocking transmurally evoked secretion than ACh‐evoked secretion of CA. Verapamil (0.1 mM) had no significant effect on secretion evoked by either procedure. A 5‐fold increase in its concentration caused about 75% blockade of secretion. 9. Differential effects of various ions and agents on CA secretion are explained on the basis that these compounds affect neurosecretory properties of the presynaptic splanchnic nerve terminals and of chromaffin cells differently.
Dissociation between stimulant‐evoked acinar membrane resistance change and amylase secretion in the mouse parotid gland.
Authors: Iwatsuki N , Petersen O H
Published: December 2014

1. Isolated segments of mouse parotid gland were superfused with a physiological saline solution. Membrane potential and input resistance were measured with intracellular micro‐electrodes. Amylase secretion was monitored using an automated fluorometric assay. The parotid gland was stimulated by exposure to isoprenaline (10(‐6)M), ACh (10(‐6) M), dibutyryl or monobutyryl cyclic AMP (10(‐3)M). 2. ACh evoked a sharp decrease in input resistance (from about 3‐6 M omega to 1‐2 M omega ) accompanied by a modest (two‐fold) increase in amylase output. Both effects were fully reversible. 3. Isoprenaline evoked a marked increase in amylase output (five to ten‐fold) reaching maximum after 20‐30 min of stimulation. Throughout the period of intensive secretion the input resistance remained at the control level. Short pulses of ACh stimulation dramatically reduced input resistance in this period. 4. Dibutyryl cyclic AMP and monobutyryl cyclic AMP caused marked increases in amylase output (five to ten‐fold) peaking 40‐50 min after start of the continuous stimulation. This increase in amylase secretion was not accompanied by any change in input resistance. Short pulses of ACh stimulation sharply and reversibly reduced input resistance both in control and test periods. 5. It is concluded that the ACh‐evoked reduction in input resistance is not a consequence of the secretory event and that secretion does not itself cause a decrease in input resistance.
Diminished response to beta‐bungarotoxin in neonatal rat diaphragm.
Authors: Gundersen C B
Published: December 2014

1. The effects of beta‐bungarotoxin on acetylcholine turnover were studied in neonatal rat diaphragms using a gas chromatographic mass spectrometric assay to measure acetylcholine and choline. 2. Injection of neonatal rats (1‐15 days old) with a fixed dose of beta‐bungarotoxin resulted in a shorter time to death in the older animals. 3. This increased lethal potency of beta‐bungarotoxin in the older rats was correlated with an enhancement of the stimulatory effect of the toxin on acetylcholine synthesis in diaphragm in vivo and in vitro. 4. The reduced effect of beta‐bungarotoxin in promoting the accumulation of acetylcholine in new‐born rat diaphragms was not due to an enhancement by the toxin of acetylcholine output from these preparations. 5. These results demonstrate that the stimulatory effect of beta‐bungarotoxin on acetylcholine synthesis in diaphragm is a function of the age of the rat. Thus, beta‐bungarotoxin may be valuable as a probe of the maturation of presynaptic function in rat skeletal muscle.
Effects of anorexigenic peptide on gastric and pancreatic secretion.
Authors: Coy D , Jaworek J , Konturek S J , Kwiecień N , Radecki T , Schally A V , Tasler J
Published: December 2014

1. Gastric and pancreatic secretion as well as serum gastrin an insulin levels have been measured after sham‐feeding, real feeding or exogenous hormonal stimulation in conscious dogs receiving (pyro) Glu‐His‐Gly, an appetite depressing peptide (AP). 2. Sham‐feeding produced a marked increase in gastric acid and pepsin outputs accompanied by an elevation of serum gastrin and insulin concentrations. AP infusion before and after sham‐feeding reduced the peak gastric secretion and suppressed gastrin and insulin responses to sham‐feeding. 3. Liver extract meal administered into the stomach resulted in an increase in gastric acid and serum gastrin and insulin levels. AP inhibited acid response to liver extract without affecting serum hormonal levels. Pentagastrin stimulation produced similar acid secretion to that obtained with liver extract and AP infusion also inhibited this secretion. 4. Secretin infusion or feeding a meat meal produced a similar rate of pancreatic bicarbonate secretion in dogs with chronic pancreatic fistula. AP infusion inhibited the bicarbonate response to feeding or secretin without affecting serum gastrin or insulin levels. 5. This study demonstrates that pyro‐Glo‐His‐Gly suppresses serum hormonal and gastric secretory response to cephalic stimulation and reduces gastrin and pancreatic secretory responses to ordinary feeding or exogenous hormonal stimuli.