bluuebunny/crossref_metadata_2025 huggingface dataset:
The interaction between noradrenaline activation and distension activation of the rabbit ear artery.
Authors: Speden R N , Warren D M
Published: December 2014

Excised, pressurized segments of the rabbit ear artery have been used to examine the interaction between the transmural pressure and constriction of arteries by extraluminal noradrenaline. The bath temperature was kept at 32‐33 degrees C to suppress instability and spontaneity of constriction. Fast, reproducible jumps in pressure were obtained by using a microcomputer to control an electropneumatic transducer. The arteries did not react actively to transmural pressure changes unless already activated by noradrenaline. Active arteries responded to distension by a pressure jump with a reproducible compensatory constriction which was unaffected by tetrodotoxin. The counteraction of distension was due primarily to enhanced activation of the muscle. Distension activation decreased with increasing constriction. Utilization of the force‐generating capacity of the arteries either remained unchanged at 20‐30% or, in one experiment, increased slightly when constriction against a transmural pressure of 60 mmHg was increased from 20 to 75% of maximal by raising the noradrenaline concentration. When the transmural pressure was 90 mmHg, the 35‐55% utilization of the force‐generating capacity either remained constant or fell as constriction was increased. Most of the force‐generating capacity was available for counteracting the distension of moderately constricted arteries (less than 40% of maximal) produced by a 60‐90 mmHg jump. More than 78% of the maximum capacity was used in attempting to overcome the distension when it was maintained by computer‐controlled increases in transmural pressure. The moderate constrictions were produced with noradrenaline concentrations which were 500‐10,000 times lower than that used to maximally activate the arteries. The rabbit ear artery possesses a powerful, distension‐sensitive mechanism that acts to minimize diameter changes initiated by transmural pressure jumps. The diameter of the active artery was determined by a combination of noradrenaline activation and distension activation for constrictions up to at least 75% of maximal. It is concluded that the interaction between noradrenaline activation and distension activation helps the muscle to fulfil the special functional requirements imposed by the geometry of tubes. This type of myogenic control system may be particularly well developed in those muscular blood vessels exposed to pulsatile internal pressures.
A phorbol ester has dual actions on the mechanical response in the rabbit mesenteric and porcine coronary arteries.
Authors: Itoh T , Kanmura Y , Kuriyama H , Sumimoto K
Published: December 2014

To clarify the role of protein kinase C in the mechanical response, the effects of 12‐o‐tetradecanoylphorbol‐13‐acetate (TPA), an activator of protein kinase C, were investigated on intact and skinned smooth muscle preparations of the rabbit mesenteric artery. TPA (0.1 microM) showed dual actions (initial enhancement followed by inhibition during long exposure) on the K+‐induced contraction. The enhancement was marked in the presence of 39 mM‐K+ but inhibition was the predominant effect in the presence of 128 mM‐K+. Addition of 2.6 mM‐Ca2+ to a Ca2+‐free solution containing 2 mM‐EGTA following application of A23187 (1 microM), produced contraction. TPA showed the same dual actions on this Ca2+‐induced contraction. In chemically skinned muscles, TPA increased the amplitude of Ca2+‐induced contractions evoked by low concentrations of Ca2+ (0.1‐0.3 microM), but reduced those evoked by high concentrations of Ca2+ (1‐10 microM). Both actions of TPA were facilitated in the presence of phosphatidylserine (PS). TPA with PS had no effect on the Ca2+‐independent contraction evoked in relaxing solution containing 10 mM‐EGTA and 4 mM‐Mg ATP following application of adenosine‐5‐o‐3‐thiotriphosphate (ATP gamma S) and 0.3 microM‐Ca2+. The amount of Ca2+ stored in cells estimated from the amplitude of the caffeine‐induced contraction was not modified by application of TPA with PS in skinned or intact muscle tissues. The effects of TPA were investigated on the Ca2+ transient measured from the intensity of fluorescence of quin‐2 in dispersed cell suspensions prepared from the porcine coronary artery. TPA had no effect on the Ca2+ transient in high K+ but enhanced the amplitude of the contraction. Amplitudes of the tonic response evoked by 39 mM‐K+ in intact muscle tissues and the contraction induced by 0.3 microM‐Ca2+ in skinned muscle were much the same. TPA with PS enhanced the amplitudes of both contractions to the same extent. From the above results, we concluded that TPA shows dual actions on the contractile machinery and may act on the regulatory systems of contractile proteins. Both excitatory and inhibitory actions of TPA depended on the concentration of Ca2+. However, the physiological action of protein kinase C as estimated from the action of TPA seems to be related to an excitatory action on the contractile machinery.
On the specificity of sensory reinnervation of cat skeletal muscle.
Authors: Collins W F , Mendell L M , Munson J B
Published: December 2014

Experiments were addressed to the following questions: when a muscle nerve is sectioned and regenerates to what extent are muscle receptors (spindles and tendon organs) reinnervated? is the reinnervation specific? that is, do group Ia and spindle group II fibres preferentially reinnervate spindles and do group Ib fibres preferentially reinnervate tendon organs? what are the consequences to the afferent of failure to re‐establish appropriate receptor innervation? In normal cats, and in cats 3, 6 or 9 months after section and resuture of the medial gastrocnemius muscle nerve, medial gastrocnemius afferent fibres in continuity were impaled in dorsal rootlets for recording and stimulation. Receptor innervation was determined electrophysiologically by manipulation of the medial gastrocnemius muscle. Afferent fibre type was determined by the presence (group Ia or spindle group II) or absence (group Ib) of field potentials in the homonymous motoneurone pool in response to activation of the afferent fibre. In normal cats, two‐thirds of recorded afferents innervated spindles; 89% of these generated field potentials detected in the motoneurone pool. One‐third of recorded afferents innervated tendon organs; none of these generated such field potentials. In operated cats, about half of the recorded afferents innervated spindles, about one‐third responded abnormally or not at all to muscle manipulation, and fewer than one‐tenth innervated tendon organs. Numbers of afferents which innervated spindles increased with time. The proportion of afferents generating field potentials was smaller in operated than in normal animals (40% vs. 60%) and declined progressively with time. Field potentials were generated by fibres in all categories of receptor reinnervation. This ability was lost at long post‐operative intervals by fibres failing to reach the muscle. Conduction velocity of fibres fell in operated animals. Fibres reinnervating their original type of receptor (e.g. group Ia fibre‐‐‐‐spindle) exhibited greater conduction velocity than fibres innervating an inappropriate receptor or no receptor. From these findings and other considerations (see Discussion) we conclude that following section and resuture of the medial gastrocnemius muscle nerve: about 75% of afferents regenerate into the medial gastrocnemius muscle, many more spindles than tendon organs become reinnervated, random populations of groups Ia and Ib (and probably spindle group II) fibres reinnervate spindles, fibres which fail to re‐establish appropriate receptor innervation also fail to recover normal conduction velocity.(ABSTRACT TRUNCATED AT 400 WORDS)
Changes in miniature end‐plate potentials due to moderate hypertonicity at the frog neuromuscular junction.
Authors: Doherty P , Hawgood B J , Smith I C
Published: December 2014

The effect of an increase in tonicity on the amplitude and frequency of miniature end‐plate potentials (m.e.p.p.s) following superfusion of 50 mM‐ or 100 mM‐sucrose‐Ringer solution was determined from intracellular recording at end‐plates of the frog cutaneous pectoris muscle, in the absence of drugs and using on‐line statistical analysis. An immediate decrease in mean amplitude of the order of 20% control was associated with a marked increase in mean frequency. A delayed increase in mean amplitude, independent of frequency, followed the initial response in the majority of end‐plates exposed to 100 mM‐sucrose‐Ringer solution. The net gain was of the order of 34% and was attained over 20‐40 min. This was not reversible over at least 20 min. There was an increase in the variability of m.e.p.p. amplitudes associated with the increase of mean amplitude but this was reversible. A moderate increase in tonicity is considered to induce two kinds of presynaptic changes. First, an immediate increase in the probability of release of smaller quantal packets and secondly, an increased loading of transmitter into vesicles within the readily releasable store.
Components of charge movement in rabbit skeletal muscle: the effect of tetracaine and nifedipine.
Authors: Lamb G D
Published: December 2014

The effects of tetracaine and nifedipine on asymmetric charge movement in rabbit muscle fibres were examined to investigate whether mammalian charge movement could be subdivided into several components. Tetracaine (0.05‐0.2 mM) stopped contraction in every sternomastoid fibre examined (n = 9) and reduced the asymmetric charge (moved by depolarizing steps to 0 mV) by 15% (S.E. of mean 3%). Tetracaine had little effect on the charge moved at potentials more negative than the threshold potential (established in the absence of the drug). Application of the Ca2+ channel blocker nifedipine (2 or 10 microM), reduced the mean maximum asymmetric charge to 50% (+/‐ 4) of the control value in twenty‐three sternomastoid fibres and to 32% (+/‐ 5) in four soleus fibres. Increasing the concentration of nifedipine to 120 microM had little further effect. The charge moved at potentials more negative than ‐60 mV was unaffected by nifedipine. A similar result was found with 30 microM‐D600 (two fibres). 10 microM‐nifedipine completely blocked Ca2+ currents (external [Ca2+] = 8 mM), but 0.15 microM‐nifedipine only had a small effect on either the Ca2+ current or charge movement in the four fibres examined. Contractions could no longer be elicited in eleven of eighteen fibres within 6 min of the application of 2 or 10 microM‐nifedipine. However, in the remaining seven fibres contractions could be elicited with unchanged thresholds over 30 min, even in the presence of 50 microM‐nifedipine. Nifedipine did not noticeably effect q gamma. It is suggested that nifedipine might prevent contraction only when, for other reasons, the normal release of Ca2+ from the sarcoplasmic reticulum has been disrupted and contraction is dependent on the inflow of external Ca2+. The amount of asymmetric charge moved by depolarizing steps was about 50% greater with a holding potential of ‐110 mV than with one of ‐90 mV. This 'extra' charge was not suppressed by nifedipine.
Are Merkel cell‐neurite reciprocal synapses involved in the initiation of tactile responses in salamander skin?
Authors: Diamond J , Holmes M , Nurse C A
Published: December 2014

In salamander skin the Merkel cell‐neurite complexes located near the base of the epidermis are the morphological correlates of the rapidly adapting touch receptors (Parducz, Leslie, Cooper, Turner & Diamond, 1977). The present electron microscopic studies revealed that these complexes contain reciprocal synapses polarized in the direction Merkel cell to neurite, and in the opposite direction, neurite to Merkel cell. The possible involvement of chemical transmission in the initiation of the mechanosensory response, was studied in vitro with the aid of a stable skin‐nerve preparation in which single mechanoreceptors were activated under controlled conditions. Mechanosensitivity was measured with a calibrated prodder (tip diameter 10‐30 micron) applied to random or selected points on the surface of the skin while the afferent impulse was recorded in the attached nerve twig. In some experiments the (tungsten) prodder was also used as a surface electrode, allowing the same mechanosensory axon to be excited mechanically (i.e. physiologically), and/or electrically. When applied at a single 'touch spot', suitably timed subthreshold mechanical and subthreshold electrical stimuli could summate to produce a single action potential. The temperature coefficient (Q10) between 5 and 15 degrees C for the latency of the afferent spike was small, in the range 1.3‐2, whether it was evoked by mechanical or electrical stimulation. The latency following the mechanical stimulus, which included the transduction step, was longer than that following the electrical stimulus by 0.5‐2.5 ms, and this additional delay was also relatively insensitive to temperature. In several cases removal of the epidermis with its Merkel cells (and presumably the most distal portions of the afferent nerve terminations) did not render the remaining skin totally insensitive to mechanical stimulation; however, the remaining receptive elements, though still rapidly adapting, generally had increased mechanosensory thresholds. The mechanosensitivity of the skin was unaffected by bath application of several aminergic (e.g. noradrenaline, 5‐hydroxytryptamine, octopamine) and purinergic (e.g. ATP, quinacrine) compounds at concentrations in the range 0.2‐2 mM. Removal of extracellular Ca2+ combined with elevation of extracellular Mg2+ (10‐40 mM) had relatively little effect on the mechanosensitivity over periods of up to 1 h. In contrast, application of Co2+ (2‐10 mM) produced a decrease or blockade of the mechanosensitivity that was not associated with any obvious alterations in the ultrastructure of the Merkel cell‐neurite complex.(ABSTRACT TRUNCATED AT 400 WORDS)
Oscillatory properties of guinea‐pig inferior olivary neurones and their pharmacological modulation: an in vitro study.
Authors: Llinás R , Yarom Y
Published: December 2014

The oscillatory properties of the membrane potential in inferior olivary neurones were studied in guinea‐pig brain‐stem slices maintained in vitro. Intracellular double‐ramp current injection at frequencies of 1‐20 Hz revealed that inferior olivary neurones tend to fire at two preferred frequencies: 3‐6 Hz when the cells were actively depolarized (resting potential less than ‐50 mV), and 9‐12 Hz when they were actively hyperpolarized (resting potential more than ‐75 mV). In 10% of the experiments spontaneous subthreshold oscillations of the membrane potential were observed. These oscillations, which resembled sinusoidal wave forms and had a frequency of 4‐6 Hz and an amplitude of 5‐10 mV, occurred synchronously in all cells tested within the slice. These oscillations persisted in the presence of 10(‐4) M‐tetrodotoxin and were blocked by Ca2+ conductance blockers or by the removal of Ca2+ from the bathing solution. The oscillations were affected by gross extracellular stimulation of the slice but not by intracellular activation of any given neurone. The data indicate that these oscillations reflect the properties of neuronal ensembles comprised of a large number of coupled elements. Similar ensemble oscillation could be induced, in most experiments, by adding harmaline (0.1 mg/ml) and serotonin (10(‐4) M) to the bath and could be blocked by bath addition of noradrenaline. Harmaline was found to increase cell excitability by hyperpolarizing the neurones and shifting the inactivation curve for the somatic Ca2+ spike to a more positive membrane potential level. The role inferior olivary oscillations play in the organization of motor coordination is discussed.
Effects of external calcium on potassium contractures in tonic muscle fibers of the frog (Rana pipiens).
Authors: Huerta M , Muñiz J , Stefani E
Published: December 2014

K+ contractures of tonic bundles from cruralis muscle of the frog were studied with different K+ concentrations (10‐120 mM). K+ contractures had an initial transient phase followed by a sustained tension. The amplitude of the sustained tension diminished with high K+ concentration (80‐120 mM). However, in all cases, tension was maintained for several minutes. External Ca2+ reduction practically abolished the sustained phase of the K+ contractures. The initial phase was also reduced and tension spontaneously relaxed. The curve relating the peak tension with log [K+]o, showed that the threshold was not affected but the peak tension was reduced to about 70% in low‐Ca2+ saline (0 Ca2+ + 3 mM‐Mg2+) and 50% in Ca2+‐free saline (1 mM‐EGTA + 3 mM‐Mg2+). The dependence of the sustained tension on external Ca2+ was further confirmed by Ca2+ withdrawal and re‐establishment and/or by Ni2+ substitution for Ca2+ before or during K+ contractures. These results indicate that external Ca2+ had to be continuously present to maintain the tension during K+ contractures and that Ni2+ was not able to restore the normal temporal course of K+ contracture. The sustained phase was diminished by blocking agents of Ca2+ channels, such as nifedipine (1 microM) and diltiazem (1‐10 microM). The present results can be explained by a direct control of the Ca2+ currents on K+ contracture or by specific interactions between external Ca2+ and Ca2+‐binding sites in the membrane.
Thyroid hormone effects on lactase expression by rat enterocytes.
Authors: Hewitt J E , Smith M W
Published: December 2014

Thyroxine (T4) and triiodothyronine (T3) injected into adult rats causes first an increase and then a decrease in lactase activity measured subsequently in intestinal homogenates of rat jejunum. These changes are not associated with any alteration in intestinal structure or enterocyte migration rate. Quantitative cytochemistry shows T4 stimulation and inhibition of lactase activity to take place in upper villus and crypt cells respectively (O‐ and C‐enterocytes). T3 injected into thyroidectomized rats produces identical stimulatory effects on lactase development to T4 injected into control animals. Radioactive T3 is distributed in all cell types following intraperitoneal injection into thyroidectomized rats. Highest amounts of recovered T3 are found in C‐ rather than O‐ enterocytes. Quantitative autoradiography shows intracellular T3 to be located in nuclear and cytoplasmic compartments following intraperitoneal injection. Simultaneous injection of non‐radioactive hormone displaces 50‐75% of radioactive T3. These results are discussed in relation to what is already known concerning the ability of thyroid hormones to affect intestinal development. The future need to study the physiological effects of T3 at the cellular level in the intestine is also emphasized.
Interaction between sodium and chloride transport in bovine tracheal epithelium.
Authors: Langridge-Smith J E
Published: December 2014

The active transport of Na and Cl across bovine tracheal epithelium was studied in vitro by measuring 22Na and 36Cl fluxes under short‐circuit conditions. Under basal conditions, both net Cl secretion and net Na absorption were observed: the sum of these two net fluxes accounted for 85% of the measured short‐circuit current. The rate of spontaneous Cl secretion exceeded that of Na absorption by a factor of 2. Indomethacin, an inhibitor of endogenous prostaglandin production, decreased Cl secretion and increased Na absorption, reversing the direction of net transepithelial ion flow from secretion to absorption. The ratio of the change in each net ion flux was about 1:1. 50% of the basal net flux of Na was inhibited by amiloride (10(‐4) M). The indomethacin‐induced increase in the lumen‐to‐serosa flux of Na was entirely amiloride sensitive. An amiloride‐insensitive fraction of this flux, of constant magnitude, was apparent in both control and indomethacin‐treated tissues. The Na transport inhibitor had no effect on unidirectional or net Cl fluxes. Cl secretion was abolished by 4‐methyl‐diphenylamine‐2'‐carboxylic acid (50B). The Cl transport inhibitor had no effect on unidirectional or net Na fluxes. The results suggest that the rates of Na and Cl transport may be modulated in a reciprocal fashion by certain agents, which probably act through cyclic AMP, but that the two transport processes are not mutually interdependent in any simple, direct fashion. The lack of evidence for direct interaction between Na and Cl transport raises the possibility that there are separate absorptive and secretory cells in the tracheal epithelium, rather than a single transporting cell.
Non‐synaptic depolarizing potentials in rat supraoptic neurones recorded in vitro.
Authors: Bourque C W , Randle J C , Renaud L P
Published: December 2014

Intracellular recordings obtained from eighty‐two supraoptic nucleus neurones in perfused explants of rat hypothalamus revealed a mean resting membrane potential of ‐66 +/‐ 5 mV (S.D.) and spike amplitudes of 70‐106 mV. When recorded with K acetate‐filled micropipettes, non‐spike membrane voltage fluctuations included spontaneous depolarizing and hyperpolarizing potentials. Spontaneous hyperpolarizing potentials peaked in 3‐5 ms and decayed exponentially with a mean time constant of 20.2 +/‐ 0.1 ms, 1.6 times the membrane time constant of 13.8 +/‐ 0.1 ms. These potentials were identified as spontaneous inhibitory post‐synaptic potentials, and all demonstrated a common reversal potential near ‐80 mV, a depolarizing shift of this reversal potential during intracellular Cl‐ accumulation, and reversible blockade by raising [Mg2+] to 15 mM in the perfusate. Depolarizing potentials with features typical of spontaneous excitatory post‐synaptic potentials i.e. brief (8‐20 ms) depolarizing transients, were rarely recorded with K acetate‐filled micropipettes. Instead, most neurones demonstrated what are termed non‐synaptic depolarizing potentials (n.s.d.p.s) lasting 20‐125 ms (mean 86.4 +/‐ 8.6 ms (S.E. of mean)) with a rise time 21.1 +/‐ 2.8 ms and a decay time of 16.3 +/‐ 2.8 ms (n = 28 measured). Unlike typical spontaneous post‐synaptic potentials, these events could sustain a constant peak amplitude for most of their duration. These n.s.d.p.s displayed a strong voltage‐dependent behaviour and were detected only at membrane potentials within 5‐7 mV of the threshold for spike initiation. Spontaneous slow depolarizing membrane shifts preceding or following phasic bursts, or any manipulation (e.g. current step, sinusoid, depolarizing after‐potential) causing the membrane potential to enter this range of activation, prompted their appearance. N.s.d.p.s were completely insensitive to the presence of 15 mM‐Mg2+ but they were reduced in size and frequency when Ca2+ were replaced with Co2+ or Mn2+. They were detected at a more positive membrane potential when Na+‐dependent action potentials were blocked with tetrodotoxin. The size, voltage‐dependent and non‐synaptic nature of these depolarizing potentials raises the possibility that they reflect the activity of individual (or small clusters of) ionic channels carrying inward current. Their ability to serve as prepotentials to trigger spikes is deemed to be particularly important for promoting the onset of phasic bursts in supraoptic neurosecretory neurones.
Mechanism of vasodilation induced by alpha‐human atrial natriuretic polypeptide in rabbit and guinea‐pig renal arteries.
Authors: Fujii K , Ishimatsu T , Kuriyama H
Published: December 2014

Effects of alpha‐human atrial natriuretic polypeptide (alpha‐HANP) on electrical and mechanical properties of smooth muscle cells of the guinea‐pig and rabbit renal arteries and of the guinea‐pig mesenteric artery were investigated. alpha‐HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea‐pig and rabbit renal arteries. In the guinea‐pig mesenteric and renal arteries, alpha‐HANP (up to 10 nM) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) of excitatory junction potentials nor on action potentials. In the guinea‐pig renal artery, alpha‐HANP (up to 10 nM) had no effect on the depolarization induced by noradrenaline (NA) (up to 10 microM) but markedly inhibited NA‐induced contraction. alpha‐HANP (10 nM) slightly inhibited the K‐induced contraction. In the rabbit renal artery, alpha‐HANP (10 nM) inhibited the NA‐induced contraction and to a lesser extent the K‐induced contraction. In the rabbit renal artery, the effects of alpha‐HANP on the release of Ca from the cellular storage by two applications of NA, and its re‐storage, were investigated in Ca‐free solution containing 2 mM‐EGTA. When 5 nM‐alpha‐HANP was applied before and during the first application of 0.5 microM‐NA, the contraction was markedly inhibited but the contraction to a second application of 10 microM‐NA was potentiated. If the first dose of NA was 10 microM the effect was very small. Under the same experimental procedures, nitroglycerine (10 microM) showed almost the same effects as alpha‐HANP on the NA‐induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca‐free solution, alpha‐HANP (5 nM) and nitroglycerine (10 microM) inhibited both contractions to the same extent. In the rabbit renal artery, applications of alpha‐HANP or nitroglycerine increased the amount of guanosine 3',5'‐phosphate (cyclic GMP) in a dose‐dependent manner. However, a much higher concentration of nitroglycerine was required (2 X 10(3) times). In the rabbit renal artery, hydrolysis of phosphatidyl inositol 4,5‐bisphosphate (PI‐P2) activated by 0.5 microM‐NA was inhibited by alpha‐HANP, in a dose‐dependent manner, but activation by 10 microM‐NA was not inhibited by alpha‐HANP (up to 100 nM).(ABSTRACT TRUNCATED AT 400 WORDS)
The effect of percutaneous motor cortex stimulation on H reflexes in muscles of the arm and leg in intact man.
Authors: Cowan J M , Day B L , Marsden C , Rothwell J C
Published: December 2014

The technique of electrical stimulation of the brain via scalp electrodes has been used to activate corticospinal pathways in intact man. The intensity of stimulation was adjusted to be below the threshold necessary to evoke a direct electromyographic response when the muscles being tested were totally relaxed. Changes in spinal cord excitability were measured using H‐reflex (monosynaptic) testing. By this means it was found that subthreshold scalp stimulation can produce a descending corticospinal volley even in the absence of a direct muscle response. The time course of changes in spinal cord excitability was evaluated by evoking test H reflexes at different intervals relative to the scalp stimulus. In wrist and finger flexor muscles of seven subjects, a single subthreshold scalp shock produced an initial peak facilitation of the H reflex which on average lasted for 2.5 ms. The end of the initial facilitation was marked by a return of the H reflex towards basal levels and on one occasion by a frank inhibition. It is suggested that the initial facilitation is produced by arrival at the motoneurones of monosynaptic excitatory post‐synaptic potentials (e.p.s.p.s) and is truncated by the subsequent arrival of disynaptic inhibitory post‐synaptic potentials (i.p.s.p.s). The initial facilitation was followed by a second phase of facilitation of the H reflex. The second phase was weaker, more variable and longer lasting (from 5 to 20 ms) than the first phase. The threshold of scalp stimulus intensity required to produce an effect on the H reflex was the same for the first and second phases of facilitation. Several possible explanations are discussed for the mechanism responsible for the late and long‐lasting facilitation. In two subjects wrist and finger extensor muscles were studied. The time course of H‐reflex changes was similar to that of the flexors except that the initial facilitation was followed by a frank inhibition in both subjects. In one subject thenar muscles and tibialis anterior were studied and behaved similarly to wrist and finger flexor muscles. Effects on the soleus H reflex was studied in seven subjects. In five of these subjects, in contrast to the other muscles studied, the initial event was an inhibition of the H reflex. This inhibition also could be seen preceding the usual period of facilitation in averaged rectified surface electromyogram (e.m.g.) records when scalp stimuli were given during weak voluntary activation of soleus.(ABSTRACT TRUNCATED AT 400 WORDS)
Modification by lung inflation of the vascular responses from the carotid body chemoreceptors and other receptors in dogs.
Authors: Daly M D , Ward J , Wood L M
Published: December 2014

The reflex effects of increasing pulmonary ventilation on the responses of the hind‐limb and systemic vascular resistances to stimulation of the carotid body chemoreceptors and carotid sinus baroreceptors and to distension of the urinary bladder have been studied in the anaesthetized dog. A preparation was used incorporating total cardiopulmonary bypass to maintain the arterial blood gas composition constant when alterations in pulmonary ventilation were made. The regions of both carotid bifurcations, the arch of the aorta and the cerebral circulation were independently perfused at constant pressure so as to exclude secondary reflexes from arterial baroreceptors. Four levels of pulmonary ventilation were used: 0.095, 0.285, 0.475 and 0.665 l min‐1 kg‐1 body weight, at a constant frequency of 19 cycles min‐1. Increasing the pulmonary ventilation per se in steps from 0.095 to 0.665 l min‐1 kg‐1 resulted in a significant progressive reduction in hind‐limb and systemic vascular resistances which were shown to be due to a reflex from the lungs. Stimulation of the carotid body chemoreceptors by hypoxic hypercapnic blood resulted in an increase in hind‐limb and systemic vascular resistances when carried out at each of the four levels of pulmonary ventilation. The size of the increases in vascular resistances, however, was progressively and significantly reduced as the pulmonary ventilation was increased. This partial inhibition of the carotid body reflex vasoconstrictor response was dependent on the innervation of the lungs. Stimulation or unloading of the carotid sinus baroreceptors by altering the perfusion pressure in the vascularly isolated carotid bifurcation regions caused a significant decrease and increase respectively in hind‐limb and systemic vascular resistances at all four levels of pulmonary ventilation. Unlike the responses to chemoreceptor stimulation, the size of these responses was unaffected by the level of pulmonary ventilation. Distension of the urinary bladder resulted in a significant increase in hind‐limb and systemic vascular resistances. The size of these responses was also unaltered by changing the level of pulmonary ventilation. These results indicate that there is an interaction between the inputs from the lungs and the carotid body chemoreceptors in the control of hind‐limb and systemic vascular resistances. In contrast the inputs from the carotid sinus baroreceptors and the urinary bladder were unaffected by the input from the lungs.
Potassium uptake in the mouse submandibular gland is dependent on chloride and sodium and abolished by piretanide.
Authors: Exley P M , Fuller C M , Gallacher D V
Published: December 2014

Nervous or hormonal stimulation of salivary secretion in vivo is associated with a pronounced efflux of K+ from the secretory, acinar cells into the blood. This K+ efflux is followed in the post‐stimulus period by a reuptake of K+ into the glandular tissue. In the present study we monitor the changes in [K+] of physiological solutions perfusing a flow chamber containing isolated segments of mouse submandibular glands. Nervous stimulation or the application of exogenous acetylcholine (ACh, 10(‐5) M) to the isolated glandular tissue results in characteristic changes in the [K+] of the superfusate, indicating net K+ release followed by K+ reuptake. The post‐stimulus reuptake of K+ is shown to be susceptible to blockade by either ouabain (10(‐3) M) or piretanide (10(‐4) M). The reuptake was markedly attenuated if Cl‐ in the superfusate was replaced by either NO3‐ or SO4(2‐). The K+ uptake was, however, unaffected when Br‐ replaced Cl‐ in the superfusate. Similar effects were observed in the unstimulated glandular tissues. The introduction of Cl‐(‐)free media containing either NO3‐ or SO4(2‐) resulted in a loss of K+ from the tissue which was followed, upon reintroduction of Cl‐, by a pronounced uptake of K+. When Br‐ was substituted for Cl‐ there was very little change in [K+] upon removal or reintroduction of Cl‐. The uptake of K+ induced by reintroduction of Cl‐ after a period of NO3‐ or SO4(2‐) superfusion was blocked by both ouabain and piretanide. This uptake of K+ was also dependent on the presence of extracellular Na+. Both Cl‐ and Na+ had to be present in the superfusing medium for K+ uptake to be fully manifest. These findings indicate that the K+ uptake observed in both the resting and stimulated submandibular gland cannot be explained as solely due to the activity of the Na+‐K+‐adenosine triphosphatase (Na+‐K+‐ATPase). The demonstrated anionic selectivity, dependence on extracellular Na+ and susceptibility to blockade by the diuretic piretanide would strongly suggest that a coupled Na+‐K+‐Cl‐ co‐transport system operates in submandibular glands as it does in other transporting epithelia to achieve K+ uptake.
Discharge patterns of cervical sympathetic preganglionic neurones related to central respiratory drive in the rat.
Authors: Gilbey M P , Numao Y , Spyer K M
Published: December 2014

The central respiratory‐drive‐related inputs to antidromically identified cervical sympathetic preganglionic neurones have been investigated, in the rat, using extracellular recording techniques, the ionophoretic application of an excitatory amino acid (glutamate) to increase their excitability, and phrenic nerve discharge as an indicator of central respiratory drive. Three distinct firing patterns of sympathetic preganglionic neurones are described: maximal discharge during phrenic nerve activity, maximal discharge during phrenic silence, and a firing pattern unrelated to phrenic nerve discharge. Both spontaneously active and glutamate‐activated silent cervical sympathetic preganglionic neurones had similar, if not identical, firing patterns. The application of glutamate, using ionophoretic currents of up to 100 nA, did not disrupt central respiratory‐drive‐related discharge patterns indicating that these inputs are an important contribution in the regulation of the firing pattern of a proportion of sympathetic preganglionic neurones. On the basis of these observations it is proposed that some sympathetic preganglionic neurones may receive central respiratory drive potentials similar to those received by respiratory motoneurones.
Passive transport and binding of lead by human red blood cells.
Authors: Simons T J
Published: December 2014

The uptake of Pb into human red blood cells has been studied using Pb buffers. Passive Pb movements can be studied conveniently when the cells are depleted of adenosine 5'‐triphosphate (ATP), to eliminate active transport, and of inorganic phosphate, to prevent precipitation of lead phosphate. Pb can cross the membrane passively in either direction. Influx and efflux show similar properties. Passive Pb transport is strongly stimulated by HCO3‐, and is reduced by replacing Cl‐ with ClO4‐. It is inhibited by low concentrations of 4‐acetamido‐4'‐isothiocyanostilbene‐2,2'‐disulphonic acid (SITS) and 4,4'‐diisothiocyanostilbene‐2.2'‐disulphonic acid (DIDS), characteristic inhibitors of anion transport. Pb uptake is unaffected by varying the external concentrations of Na+, K+ and Ca2+. When Pb enters the cell, it binds mainly to haemoglobin. The ratio of bound Pb:free Pb2+ in the cytosol is estimated to be 6000:1. Pb binding to haemoglobin is unaffected by oxygenation. Binding to albumin is quantitatively similar to binding to haemoglobin. The implications of these results for the transport and binding of Pb in the blood are discussed.
Electrogenic anion secretion in cultured rat epididymal epithelium.
Authors: Cuthbert A W , Wong P Y
Published: December 2014

Primary monolayer cultures enriched with principal cells from rat cauda epididymis were grown on pervious supports until confluence was reached. The epithelia so formed were used for short‐circuit current recording. Epididymal monolayers had a transepithelial potential of 0.2 mV (apical side negative), a basal short‐circuit current of 2 microA/cm2 and a transepithelial resistance of 60‐90 omega cm2 when bathed on both sides with Krebs‐Henseleit solution at 37 degrees C and gassed with 95% O2‐5% CO2. 8‐bromo‐adenosine 3',5'‐phosphate (1 mM) and forskolin (10 microM) caused an inward‐flowing current in short‐circuited monolayers. The current was partially sensitive to acetazolamide and to frusemide, suggesting that anion secretion was responsible for the responses. In the absence of chloride in the bathing fluid the response to forskolin was sensitive to acetazolamide but not to frusemide. The peptide lysylbradykinin (LBK) and prostaglandin E2 (PGE2) also produced inward‐flowing currents which again appeared to be due to anion secretion. The actions of PGE2 were seen only when this agent was added to the basolateral side of the tissue, while LBK had effects from both sides. The responses to kinin, but not to PGE2, were inhibited by cyclo‐oxygenase inhibitors such as piroxicam and indomethacin. It seems the kinin effects are dependent, at least in part, upon eicosanoid formation. Responses to kinin and PGE2 were severely attenuated in chloride‐free bathing solution. Readdition of chloride‐containing solution restored the responses to both agents. Assuming electrogenic ion secretion in the epididymis is accompanied by osmotic fluid flow it is evident that the transit time of sperm in the cauda epididymis will be reduced. Possible consequences for the maturation of spermatozoa are discussed.
The pattern of sympathetic neurone activity during expiration in the cat.
Authors: Bachoo M , Polosa C
Published: December 2014

The properties of sympathetic preganglionic neurone activity during expiration were studied in pentobarbitone‐anaesthetized (n = 26) and in non‐anaesthetized, mid‐collicular decerebrate (n = 5), paralysed, artificially ventilated cats in which the electrical activity of the phrenic nerve and of the cervical sympathetic trunk was recorded. In control conditions (end‐tidal PCO2 between 35 and 40 mmHg, zero end‐expiratory pressure) sympathetic activity during expiration was either steady at a low level (n = 11) or showed a modest progressive increase from a low level in early expiration (n = 17). Very infrequently (n = 3), it showed a transient increase during the second half of expiration. Artificial ventilation with positive end‐expiratory pressures in the range from 2.1 +/‐ 0.4 (mean +/‐ S.D.) to 6.7 +/‐ 0.6 cmH2O caused, in cats with intact vagus nerves, an increase in sympathetic neurone activity during the second half of expiration. Within this range of pressures, the magnitude of the increase was related to the magnitude of the positive end‐expiratory pressure. This effect reversed at higher positive end‐expiratory pressures. Pressures in excess of 10.2 +/‐ 1.8 cmH2O caused inhibition of sympathetic activity. The sympatho‐excitatory effect of positive end‐expiratory pressure disappeared after bilateral cervical vagotomy. With intact vagus nerves, it also disappeared at levels of systemic hypocapnia (end‐tidal PCO2 less than or equal to 15 mmHg) which abolished phrenic nerve activity. In hypocapnia, artificial ventilation with peak tracheal pressures greater than 7.2 +/‐ 1.1 cmH2O caused inhibition of sympathetic activity, while ventilation with lower end‐expiratory pressures had no effect on sympathetic activity. It may be concluded that the sympatho‐excitatory effect of positive end‐expiratory pressure is mediated by vagal afferents and requires a certain level of brain‐stem respiratory neurone activity. Sympatho‐excitation during expiration was also observed, in normocapnic conditions, during short‐duration static lung inflation with tracheal pressures in the range from 2.5 +/‐ 0.3 to 7.0 +/‐ 0.8 cmH2O as well as during artificial ventilation with zero end‐expiratory pressure when lung inflation occurred in expiration. These responses were abolished by bilateral cervical vagotomy and during systemic hypocapnia. Sympatho‐excitation during expiration was also observed when systemic hypercapnia was produced in vagotomized cats by artificial ventilation with gas mixtures containing 5 or 10% CO2.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of chlorpromazine and phencyclidine on mouse C2 acetylcholine receptor kinetics.
Authors: Changeux J P , Pinset C , Ribera A B
Published: December 2014

Patch‐clamp techniques were used to record acetylcholine‐ (ACh) activated single‐channel currents in cell‐attached membrane patches from myotubes of the mouse cell line, C2. The effects of the phenothiazine derivative chlorpromazine (CPZ) and of the hallucinogen phencyclidine (PCP) on ACh‐activated single‐channel properties were studied under conditions where both compounds are positively charged (pH 7.2). The single‐channel conductance was unaffected by either CPZ or PCP at concentrations ranging from 10 to 500 nM. 10‐200 nM‐CPZ and PCP led to shortened mean burst times. CPZ and PCP effects on mean burst times were voltage independent and did not vary in a simple linear manner with concentration. 10‐200 nM‐CPZ and PCP did not reduce channel opening frequencies, suggesting that the fraction of non‐conducting state (occupied, blocked or desensitized) favoured at equilibrium was not significant at these concentrations. On the other hand, concentrations of CPZ and PCP higher than 300 nM did lead to depressed channel opening frequencies. In addition, we observed that, at these concentrations, the shortened burst duration reverses to the longer values found at lower effector concentrations. The effects of CPZ and PCP on ACh‐activated single‐channel kinetics are interpreted in terms of current models of ACh‐receptor structure and conformational transitions.
Effects of synthetic adrenocorticotrophin on adrenal medullary responses to splanchnic nerve stimulation in conscious calves.
Authors: Edwards A V , Hansell D , Jones C T
Published: December 2014

Right medullary and various cardiovascular responses to stimulation of the peripheral end of the splanchnic nerve have been investigated in the presence and absence of exogenous adrenocorticotrophin, ACTH1‐24, (5 ng min‐1 kg‐1). The adrenal‐clamp technique was employed in conscious calves, after the pituitary stalk had been cauterized and they had recovered from anaesthesia. The intravenous infusion of ACTH1‐24 increased the plasma ACTH concentration by about 1100 pg ml‐1 and right adrenal venous output of cortisol by about 400 ng min‐1 kg body weight‐1. Stimulation of the splanchnic nerve at 4 Hz for 10 min had no effect on either arterial plasma ACTH concentration or the adrenal output of cortisol. Closely similar amounts of both adrenaline and noradrenaline were released in response to nerve stimulation in the presence and absence of exogenous ACTH. In contrast, the fall in adrenal vascular resistance of about 40%, which normally occurred in response to splanchnic nerve stimulation, was completely abolished by ACTH. The adrenal produced relatively large quantities of met‐enkephalin‐containing peptides. During splanchnic nerve stimulation the output of these increased 2‐100‐fold, at which time free met5‐enkephalin accounted for only 10‐20% of total. During ACTH infusion the output of free met5‐enkephalin was reduced at rest and during nerve stimulation, but that of total met‐enkephalin‐containing peptides was unaffected. These results indicate that ACTH or an adrenal steroid may alter the processing of proenkephalin in the adrenal medulla acutely but not total opiate secretion. Alternatively, the presence of ACTH could act by influencing the population of chromaffin cells activated by splanchnic nerve stimulation.
Small intestinal motility and transit by electromyography and radiology in the fasted and fed pig.
Authors: Rayner V , Wenham G
Published: December 2014

The pattern of small intestinal digesta transit was studied in six young pigs (20‐30 kg) by simultaneous electromyography and radiology. Pigs showed migrating myoelectric complexes (m.m.c.s) in the small intestine both when fasted and after feeding. The m.m.c.s were modified by feeding; quiescence was much reduced in duration and irregular spiking activity (i.s.a.) was prolonged; m.m.c.s were not disrupted and phases of regular spiking activity (r.s.a.) were still seen after feeding. The r.s.a. phase could be recognized on the screen and in spot films from both fasting and fed pigs as a band of intense rhythmic contractions pinching off the intestine and propelling all intestinal contents ahead of it. The r.s.a. moved caudad clearing the small intestine of digesta and leaving an empty quiescent intestine behind it. It was particularly characteristic in the fasted pig where it was usually associated with the progression of a gas bubble. The pattern of m.m.c.s in both fasted and fed animals along with the intermittent nature of stomach emptying, divided digesta into batches which progressed through the small intestine. Each batch‐‐propelled by a m.m.c.‐‐normally took 180‐190 min to pass through the small intestine. M.m.c.s had a cycle length of 70‐115 min in different parts of the small intestine. Usually two or three m.m.c.s and batches of intestinal contents were present in the small intestine at any one time. 22‐33% of the m.m.c.s faded out in the proximal ileum. Batches of digesta propelled by these m.m.c.s had transit times increased by one m.m.c. duration and fused with the subsequent batch. Sometimes new m.m.c.s were generated in the terminal ileum. Two patterns of transport into the large intestine were seen. Usually digesta was transported by peristaltic rushes starting 100‐200 cm from the ileo‐caecal junction. The rush then continued through 1‐1 1/2 turns of the spiral colon; occasionally the terminal ileum emptied by slow peristalsis. In this case there was no colonic rush and digesta went into the caecum.