bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of epidural anaesthesia with 1% lidocaine on the pressor response to dynamic exercise in man.
Authors: Friedman D B , Brennum J , Sztuk F , Hansen O B , Clifford P S , Bach F W , Arendt‐Nielsen L , Mitchell J H , Secher N H
Published: December 2014

1. In order to examine the sensitivity to local anaesthetics of afferent neural feedback from working muscle during dynamic exercise, sixteen subjects cycled for 12 min before and after epidural anaesthesia using 1% lidocaine. The presence of afferent neural blockade was verified by elimination of the blood pressure response to a cold pressor test, laser‐induced evoked potentials and increases in pain detection and tolerance thresholds of the foot. Conversely, epidural anaesthesia had no effect on these variables in the unblocked skin areas or on electrically evoked potentials in blocked or unblocked skin. 2. During dynamic exercise, heart rate increased as did mean arterial pressure and cardiac output. Mean arterial pressure remained at the exercise level during post‐exercise ischaemia, but heart rate and cardiac output decreased while total peripheral resistance increased. Epidural anaesthesia did not significantly affect these variables during rest, dynamic exercise, post‐exercise ischaemia or recovery. 3. The results of this study show that, in order to affect blood pressure during dynamic exercise, epidural anaesthesia must block the pressor response to post‐exercise ischaemia. The implication of these data is that complete or almost complete block of group III and/or group IV muscle afferents is necessary to inhibit the pressor response to dynamic exercise in man.
Calcium channel currents recorded from isolated myocytes of rat basilar artery are stretch sensitive.
Authors: Langton P D
Published: December 2014

1. Conventional and perforated patch whole‐cell methods were used to measure Ca2+ channel currents from isolated rat basilar arterial myocytes in response to voltage steps. Peak currents measured in response to repeated steps to +2 mV increased over the first 3 min after gaining whole‐cell access. The increase followed an exponential time course, was not due to decrease in underlying outward current and was independent of the presence of ATP and GTP in the pipette filling solution. 2. Application of positive and negative pressure to the pipette resulted in significant increase and decrease in peak inward current, respectively. Membrane stretch, associated with changes in cell volume, rather than applied pressure per se appeared to determine changes in peak current. 3. Using amphotericin B perforated patch recording, changes in cell volume on application of 80% hypo‐ or 120% hyperosmotic superfusing solutions were found to effect similarly peak inward current. Hyposmotically induced cell swelling increased and hyperosmotic cell shrinkage decreased peak inward current at all test potentials studied. 4. The increase in inward current in response to hyposmotic superfusate was reversible and appears to reflect an increase in voltage‐dependent Ca2+ channel current since it was not due to a change in non‐voltage‐sensitive conductance(s) and it was as sensitive as the control current to the dihydropyridine (DHP) antagonist (‐)202‐791.
Enteric GABA‐containing nerves projecting to the guinea‐pig inferior mesenteric ganglion modulate acetylcholine release.
Authors: Parkman H P , Stapelfeldt W H , Williams C L , Lennon V A , Szurszewski J H
Published: December 2014

1. The effect of GABA and GABA receptor‐modulating drugs on release of [3H]acetylcholine was studied in the guinea‐pig inferior mesenteric ganglion. 2. GABA caused a dose‐dependent increase in [3H]acetylcholine release during stimulation of the lumbar colonic nerves. Muscimol (10 microM) and diazepam (5 microM) also increased [3H]acetylcholine release during stimulation of the lumbar colonic nerves whereas baclofen (10 microM) had no effect. 3. Bicuculline (20‐100 microM) and picrotoxin (50 microM) alone reduced [3H]acetylcholine release during electrical stimulation of the lumbar colonic nerves whereas phaclofen (300 microM) had no effect. 4. Bicuculline (100 microM) significantly decreased whereas diazepam (5 microM) significantly increased distension‐induced [3H]acetylcholine release. 5. Colonic distension significantly increased [3H]GABA release in the inferior mesenteric ganglion compared to basal periods when the colon was not distended. Distension‐induced release of [3H]GABA resulted from active neuronal transmission from the colon to the inferior mesenteric ganglion, since perfusion of the inferior mesenteric ganglion with tetrodotoxin (1 microM) reduced basal release of [3H]GABA and abolished distension‐evoked increases in the release of [3H]GABA. 6. In contrast to its excitatory effects on peripheral colonic afferent cholinergic nerves, exogenous GABA caused a dose‐dependent decrease in [3H]acetylcholine release during electrical stimulation of the central lumbar splanchnic nerves. Baclofen (10 microM) also inhibited [3H]acetylcholine release whereas muscimol (10 microM) or diazepam (5 microM) had no effect. Phaclofen (300 microM) antagonized the inhibitory effects of exogenous GABA (10 microM) and of baclofen (10 microM). Bicuculline (100 microM), picrotoxin (50 microM) and phaclofen (300 microM) alone had no effect on [3H]acetylcholine release during splanchnic nerve stimulation. 7. Phaclofen (300 microM) increased [3H]acetylcholine release during simultaneous electrical stimulation of the lumbar colonic nerves and splanchnic nerves and when GABAA receptors were blocked by bicuculline (20 microM). 8. The data suggest that GABAA receptors facilitate release of acetylcholine from peripheral cholinergic mechanosensory nerves projecting from the colon to the inferior mesenteric ganglion and that GABAB receptors inhibit release of acetylcholine from central cholinergic nerves. Enteric GABA‐containing nerves projecting to the inferior mesenteric ganglion are mechanosensory. Endogenous release of GABA may act on GABAA receptors to facilitate peripheral cholinergic mechanosensory transmission and/or on GABAB receptors to inhibit central cholinergic transmission.
Hypothalamic modulation of splenic natural killer cell activity in rats.
Authors: Katafuchi T , Ichijo T , Take S , Hori T
Published: December 2014

1. The cytotoxic activity of splenic natural killer cells measured by a standard chromium release assay in urethane and alpha‐chloralose‐anaesthetized rats was significantly suppressed 20 min after bilateral ablation of the medial part of the preoptic hypothalamus (MPO). The suppression was completely blocked by prior splenic denervation. The splenic natural killer cell activity of MPO sham‐lesioned rats or thalamus‐lesioned rats, both having an intact splenic innervation, were not different from that of a non‐treated control group. 2. Electrical stimulation of the bilateral MPO (0.1 ms, 0.1‐0.3 mA, 5‐100 Hz) suppressed the efferent activity of the splenic nerve in all six rats examined. The reduction of the nerve activity was accompanied by a transient fall in blood pressure. An I.V. injection of phenylephrine (3 micrograms/0.3 ml) also evoked a suppression of the nerve activity, which was accompanied by transient hypertension, suggesting that the suppressive effect of the MPO stimulation was independent of changes in blood pressure. On the other hand, a bilateral lesion of the MPO resulted in a sustained increase in the electrical activity of the splenic sympathetic nerve filaments which lasted for more than 2 h. 3. Microinjection of monosodium‐L‐glutamate (0.1 and 0.01 M in 0.1 microliters saline) unilaterally into the MPO evoked a transient suppression of the efferent discharge rate of the splenic nerve activity within 1 min, which was also accompanied by a decrease in blood pressure. The injection of saline (0.1 microliter) into the MPO had no effect. The microinjection of recombinant human interferon‐alpha (200 and 2000 U in 0.1 microliter saline) into the MPO dose dependently increased the splenic nerve activity without any change in blood pressure. 4. In contrast, microinjection of interferon‐alpha into the paraventricular nucleus of the hypothalamus (PVN) had no effect on splenic nerve activity, although an injection of glutamate increased the nerve activity. 5. The present results, taken together with previous reports, suggest that the neuronal networks between the MPO and the splenic sympathetic nerve, which may be activated by centrally administered interferon‐alpha, are important in the suppression of the splenic cellular immunity.
Motoneuronal output and gradation of effort in attempts to contract acutely paralysed leg muscles in man.
Authors: Gandevia S C , Macefield V G , Bigland‐Ritchie B , Gorman R B , Burke D
Published: December 2014

1. The study was designed to determine the degree to which normal subjects can control motoneurones innervating a leg muscle when acutely deprived of muscle afferent feedback. Microneurographic recordings were made from eighteen motor fascicles in the common peroneal nerve, of which thirteen innervated tibialis anterior and five toe dorsiflexor muscles. The nerve was then blocked completely at a distal site near the fibular head with local anaesthetic. A sequence of tests was performed with each fascicle to determine the degree to which the subject could control the motoneuronal drive to the paralysed muscle. 2. During a complete distal block of the common peroneal nerve, motoneurones innervating tibialis anterior were frequently activated during weak attempted contraction of the synergist toe extensors and vice versa. 3. When subjects attempted contractions of the paralysed muscles at a constant effort, pressure applied to the dorsum of the foot caused relatively small changes in the level of neural output, producing a small increase in motoneuronal drive to tibialis anterior, but no consistent change in the drive to toe extensor fascicles. 4. Subjects were able to increase the motoneuronal drive to the paralysed tibialis anterior in five steps of effort each lasting 10 s. The level of motor output increased linearly with step number, but declined as the step was maintained, more so when auditory feedback was withdrawn. 5. There was hysteresis in the relationship between motoneuronal output and force (measured on the contralateral side) during attempts to make slowly increasing then decreasing ramps of effort on both sides over 20‐120 s. Motor drive to the paralysed muscle increased disproportionately rapidly compared with contralateral force when subjects attempted bilaterally symmetrical increasing efforts. 6. Subjects attempted to activate the paralysed muscle group maximally for 20‐30 s with auditory feedback of the neurogram and verbal encouragement. There was a small statistically significant reduction in the motoneuronal output 5‐10 s into the 30 s effort but, with further encouragement, it recovered towards the end of the effort. 7. When compared directly in the same recording sequences, attempts to make rapid brief maximal efforts (2‐3 s duration) produced the same motoneuronal output as attempts to make sustained efforts. 8. Similar results occurred when the motoneuronal output to tibialis anterior was recorded during a selective distal block of tibialis anterior sparing toe dorsiflexors.(ABSTRACT TRUNCATED AT 400 WORDS)
Corticocortical inhibition in human motor cortex.
Authors: Kujirai T , Caramia M D , Rothwell J C , Day B L , Thompson P D , Ferbert A , Wroe S , Asselman P , Marsden C D
Published: December 2014

1. In ten normal volunteers, a transcranial magnetic or electric stimulus that was subthreshold for evoking an EMG response in relaxed muscles was used to condition responses evoked by a later, suprathreshold magnetic or electric test shock. In most experiments the test stimulus was given to the lateral part of the motor strip in order to evoke EMG responses in the first dorsal interosseous muscle (FDI). 2. A magnetic conditioning stimulus over the hand area of cortex could suppress responses produced in the relaxed FDI by a suprathreshold magnetic test stimulus at interstimulus intervals of 1‐6 ms. At interstimulus intervals of 10 and 15 ms, the test response was facilitated. 3. Using a focal magnetic stimulus we explored the effects of moving the conditioning stimulus to different scalp locations while maintaining the magnetic test coil at one site. If the conditioning coil was moved anterior or posterior to the motor strip there was less suppression of test responses in the FDI. In contrast, stimulation at the vertex could suppress FDI responses by an amount comparable to that seen with stimulation over the hand area. With the positions of the two coils reversed, conditioning stimuli over the hand area suppressed responses evoked in leg muscles by vertex test shocks. 4. The intensity of both conditioning and test shocks influenced the amount of suppression. Small test responses were more readily suppressed than large responses. The best suppression was seen with small conditioning stimuli (0.7‐0.9 times motor threshold in relaxed muscle); increasing the intensity to motor threshold or above resulted in less suppression or even facilitation. 5. Two experiments suggested that the suppression was produced by an action on cortical, rather than spinal excitability. First, a magnetic conditioning stimulus over the hand area failed to produce any suppression of responses evoked in active hand muscles by a small (approximately 200 V, 50 microsecond time constant) anodal electric test shock. Second, a vertex conditioning shock had no effect on forearm flexor H reflexes even though responses in the same muscles produced by magnetic cortical test shocks were readily suppressed at appropriate interstimulus intervals. 6. Small anodal electric conditioning stimuli were much less effective in suppressing magnetic test responses than either magnetic or cathodal electric conditioning shocks.(ABSTRACT TRUNCATED AT 400 WORDS)
Theophylline affects three different potassium currents in dissociated rat cortical neurones.
Authors: Munakata M , Akaike N
Published: December 2014

1. The effects of theophylline in pyramidal neurones acutely dissociated from the rat frontal cortex were investigated in the whole‐cell configuration, using the nystatin‐perforated patch‐clamp technique. 2. Ten millimolar theophylline evoked triphasic responses: a small slow outward current (Iso), then a large transient outward current (Ito) and finally a slow sustained inward current (Isi). The reversal potentials of the three current components shifted 56‐58 mV for a 10‐fold change in extracellular K+ concentration, thereby indicating that all these current components were predominantly carried by K+. 3. Iso had no voltage dependence, whereas Ito showed a steep outward rectification. Iso was relatively resistant to tetraethylammonium (TEA) with an IC50 of 10 mM. Ito was susceptible to submillimolar TEA with an IC50 of 0.8 mM. 4. Isi was a net inward current mainly resulting from suppression of the M‐current (IM). 5. These three current components had a distinct concentration dependence; in particular, Isi was evoked at a relatively lower concentration range. 6. Ito was not observed when the intracellular Ca2+ was chelated by 1,2‐bis(O‐aminophenoxy)ethane‐N,N,N',N'‐tetraacetic acid (BAPTA) of 10 mM, using the conventional whole‐cell recording configuration, whereas both Iso and Isi were retained but gradually diminished. 7. In Ca(2+)‐free external solution, these responses were fully elicited by the first application of theophylline. However, Ito disappeared during successive applications and Iso, but not Isi, also decreased. Similar results were obtained in the presence of ryanodine. 8. Theophylline apparently affects three different kinds of K+ currents in rat cortical neurones. Both Iso and Ito depend on internal calcium mobilized from an intracellular Ca2+ store by theophylline, while Isi was not primarily mediated by a change in [Ca2+]i.
Adenosine‐activated potassium current in smooth muscle cells isolated from the pig coronary artery.
Authors: Dart C , Standen N B
Published: December 2014

1. The perforated patch technique with nystatin or amphotericin was used to record whole cell currents activated by adenosine in smooth muscle cells isolated enzymatically from pig coronary arteries. 2. Adenosine (5‐40 microM) activated an outward current at a holding potential of 0 mV in 5 mM [K+]o and an inward current at ‐60 mV in 143 mM [K+]o. The dependence of the reversal potential for the adenosine‐activated current on [K+]o suggests that it flows through K+ channels, while its current‐voltage relation is consistent with the channels showing little voltage dependence. 3. The adenosine‐activated current was inhibited by the sulphonylurea glibenclamide (5 microM) and by phencyclidine (5 microM). It was unaffected by charybdotoxin (50 nM) or apamin (100 nM), blockers of large and small conductance Ca(2+)‐activated K+ channels respectively. 4. At ‐60 mV in 143 mM K+ solution, openings of single channels passing a current of just over ‐2 pA could sometimes be detected in the absence of adenosine. Openings became more frequent after the application of adenosine, with several levels then being detected. Openings of channels with a larger conductance were sometimes also seen in the presence of adenosine. Fluctuation analysis gave somewhat lower estimates of unitary current than did direct measurements. 5. The effect of adenosine could be mimicked by the A1 receptor agonist CCPA (2‐chloro‐N6‐cyclopentyladenosine), while the A2 agonist CGS 21680 (2‐p‐(2‐carboxethyl)phenethylamino‐5'‐N‐ethylcarboxamido adenosine hydrochloride) was without effect. The response to adenosine was inhibited by the A1 antagonist DPCPX (8‐cyclopentyl‐1,3‐dipropylxanthine), but was unaffected by the A2 antagonist CGS 15943A (5‐amino‐9‐chloro‐2‐(2‐furanyl)‐1,2,4‐ triazolo[1,5‐C]quinazoline monomethanesulphonate). 6. Our results suggest that adenosine acts at an A1 receptor to activate K+ channels. We consider it most likely that these are ATP‐dependent K+ channels. We discuss the mechanism by which K+ channel activation may lead to hyperpolarization and so vasorelaxation.
Effects of axotomy or target atrophy on membrane properties of rat sympathetic ganglion cells.
Authors: Sánchez‐Vives M V , Gallego R
Published: December 2014

1. The electrical properties of rat superior cervical ganglion cells were examined in vitro with intracellular microelectrodes after axotomy or atrophy of the submandibular salivary gland. 2. Membrane time constant, input resistance and excitatory synaptic potentials (EPSPs) were decreased to about 50% of their control values 7‐10 days after axotomy. 3. Axotomized ganglion cells also showed reduced action potentials and after‐hyperpolarizations (AHPs). The AHP duration was reduced to 40% of the control value. 4. In 25% of the axotomized cells, the action potential was followed by an after‐depolarization (ADP) instead of the AHP that was always present in control cells. In eleven out of seventeen axotomized cells with ADP, preganglionic stimulation failed to evoke an EPSP, whereas the failure of the synaptic response was never observed in control cells and occurred only in two of fifty‐three axotomized cells with AHP. 5. In some axotomized cells with AHP, a depolarizing potential developed after a train of action potentials. This was never observed in control cells. 6. Sympathetic neurones innervating the submandibular gland in control animals had membrane properties similar to those observed in other ganglion cells. 7. The properties of neurones innervating the submandibular gland remained unaltered after the experimentally induced atrophy of the gland. 8. It is concluded that the marked effects of short‐term axotomy on membrane properties of sympathetic ganglion cells are not reproduced by long‐term atrophy of the target tissue.
Birefringence changes associated with isometric contraction and rapid shortening steps in frog skeletal muscle fibres.
Authors: Irving M
Published: December 2014

1. Muscle birefringence, the difference between the refractive indices of light polarized parallel and perpendicular to the muscle fibre axis, was measured at 3 degrees C in intact single fibres isolated from frog muscle. Resting birefringence was 2.20 +/‐ 0.02 x 10(‐3) (mean +/‐ S.E.M., n = 44) at sarcomere length 2.4‐2.7 microns and 2.35 +/‐ 0.03 x 10(‐3) (n = 19) at 3.5‐3.8 microns. 2. Birefringence decreased during isometric twitch or tetanic contractions. The peak change in a twitch at sarcomere length 2.6 microns, determined by two independent methods, was 0.150 +/‐ 0.017 x 10(‐3) (mean +/‐ S.E.M., n = 6). The corresponding value after 0.4 s of tetanic stimulation was 0.167 +/‐ 0.012 x 10(‐3) (n = 6). 3. The birefringence change had a shorter latency than tension and reached its half‐maximum value earlier than tension. The difference in time to half‐maximum in tetani was 11.5 +/‐ 1.3 ms (mean +/‐ S.E.M., n = 6) at 3 degrees C. After stimulation birefringence recovered to its pre‐stimulus baseline more slowly than tension. 4. The birefringence decrease after 0.4 s of tetanic stimulation was linearly related to the expected degree of overlap between actin and myosin filaments in the sarcomere length range 2.6‐3.6 microns. The amplitude of the birefringence decrease at full filament overlap (sarcomere length 2.2 microns) was estimated to be 0.235 +/‐ 0.015 x 10(‐3). 5. Birefringence changes associated with shortening steps of 0.9% fibre length at sarcomere length 2.6 microns exhibited four phases corresponding to those of the tension transient. There was no consistent birefringence change during the length step itself. During the rapid tension recovery birefringence increased by 0.014 +/‐ 0.001 x 10(‐3) (n = 3), measured from the end of the length step to 2 ms later. Birefringence continued to increase as tension recovery slowed, reaching a peak about 10 ms after the step, then recovered with a rate similar to that of the final tension recovery. 6. These birefringence changes are likely to be caused by axial rotation of the head domain of the myosin cross‐bridge. During isometric contraction heads bind to actin with their long axes more perpendicular to the fibre axis than in resting muscle, although there is likely to be a wide range of head orientations during contraction.(ABSTRACT TRUNCATED AT 400 WORDS)
Changes in sodium and calcium channel activity following axotomy of B‐cells in bullfrog sympathetic ganglion.
Authors: Jassar B S , Pennefather P S , Smith P A
Published: December 2014

1. Currents mediated by Ca2+ channels using Ba2+ as a charge carrier (IBa), Na+ currents (INa) and voltage‐ and Ca(2+)‐dependent K+ currents (IC) were recorded from bullfrog paravertebral sympathetic ganglion B‐cells using whole‐cell patch‐clamp recording techniques. Currents recorded from control cells were compared with those from axotomized cells 13‐15 days after transection of the postganglionic nerve. 2. Axotomy reduced peak IBa at ‐10 mV (holding potential = ‐80 mV) from 3.3 +/‐ 0.3 nA (n = 42) to 1.7 +/‐ 0.1 nA (n = 39, P < 0.001). Tail IBa at ‐40 mV following a step to +70 mV from a holding potential of ‐80 mV was also reduced in axotomized neurones (9.7 +/‐ 0.6 nA for forty‐two control neurones and 5.2 +/‐ 0.3 nA for thirty‐nine axotomized neurones; P < 0.001). Minimal changes were observed in the kinetics of activation and deactivation. 3. Pharmacological experiments using 1,4‐dihydro‐2,6‐dimethyl‐3‐nitro‐4‐(2‐ trifluoromethylphenyl)‐pyridine‐5‐carboxylic acid methyl ester (BayK 8644), nifedipine and omega‐conotoxin showed that axotomy predominantly affected the N‐type Ca2+ channels which carry the majority of ICa in these neurones. L‐type Ca2+ current was little affected and T‐type Ca2+ currents were not observed in control or axotomized cells. 4. Development of inactivation of 0 mV and recovery from inactivation of IBa at ‐80 mV exhibited three distinct components in both control and axotomized neurones: ‘fast’, ‘intermediate’ and 'slow’. The relative proportions of both the ‘fast’ and ‘intermediate’ components of inactivation at 0 mV were almost doubled after axotomy (fast component was 15% in control and 29% in axotomized neurones; intermediate component was 17% in control and 26% in axotomized neurones). ‘Fast’ and ‘intermediate’ inactivation tended to develop more rapidly and recover more slowly after axotomy. The rate of onset of 'slow’ inactivation was unaffected by axotomy but the steady‐state level at ‐40 mV was increased. Most of the change in IBa properties may be secondary to enhanced inactivation associated with axotomy. 5. Axotomy reduced IC (measured at the end of a 3 ms step from ‐40 to +20 mV) from 34.5 +/‐ 4.9 (n = 26) to 19.2 +/‐ 1.5 nA (n = 49, P < 0.005). This reduction may be secondary to the reduction in calcium channels available for activation from ‐40 mV following axotomy. 6. The TTX‐sensitive and TTX‐insensitive components of peak Na+ conductance (GNa) were both increased after axotomy. Total GNa was increased from 184.9 +/‐ 8.4 to 315.2 +/‐ 16.4 nS (n = 37 for both P < 0.001). Most of the kinetic and steady‐state properties of INa were unchanged after axotomy.(ABSTRACT TRUNCATED AT 400 WORDS)
Reflex responses to stimulation of mechanoreceptors in the left ventricle and coronary arteries in anaesthetized dogs.
Authors: al‐Timman J K , Drinkhill M J , Hainsworth R
Published: December 2014

1. Previous work has shown that physiological increases in mean aortic root pressure, which change the pressure in both the coronary circulation and the left ventricle, result in reflex vasodilatation. This study was undertaken to attempt to localize the reflexogenic area mainly responsible for the reflex. 2. In anaesthetized, artificially ventilated dogs, cannulae connected to perfusion systems were inserted in the ascending aorta, left ventricular apex and left atrium. This allowed us to change the pressures in: (a) the aortic root including both the coronary arteries and the left ventricle; (b) aortic root and coronary arteries, at constant ventricular pressure; and (c) in the ventricle, with mean (although not pulse) aortic pressure constant. Aortic and carotid baroreceptors were perfused at constant pressure and reflex responses were determined from changes in perfusion pressures (flows constant) to a vascularly isolated hindlimb and to the remainder of the systemic circulation. 3. Combined changes in mean aortic root (coronary arterial) and ventricular systolic pressures consistently resulted in decreases in perfusion pressures. A change in only mean aortic root (coronary arterial) pressure, with ventricular pressure constant, also resulted in decreases in perfusion pressures and these were only a little smaller than those to the combined stimulus. Changes in ventricular systolic pressure resulted in responses averaging only about 30% of those to the combined stimulus. 4. Setting mean aortic root or ventricular systolic pressures at different levels did not affect the responses to changes in pressures in the other region. 5. These results show that physiological increases in pressure in the aortic root and coronary arteries, in the absence of changes in pressure in the left ventricle, cause reflex vasodilatation. The relatively small response occurring when ventricular pressure was changed could be due either to a contribution from ventricular receptors or to a change in the stimulus to coronary receptors resulting from changes in the ventricular or aortic pulse. 6. We conclude that the reflex effects of increases in mean aortic root pressure are due mainly to stimulation of coronary arterial baroreceptors.
Afferent discharges from coronary arterial and ventricular receptors in anaesthetized dogs.
Authors: Drinkhill M J , Moore J , Hainsworth R
Published: December 2014

1. Previous work has shown that increases in aortic root pressure result in reflex vasodilation, and that this response is likely to result mainly from stimulation of receptors in the coronary arteries, although contribution from left ventricular receptors was not excluded. This investigation was undertaken to resolve this question and to determine the afferent nerve fibres likely to be involved in this reflex. 2. In chloralose‐anaesthetized dogs a perfusion circuit was used which allowed us to change the pressures in: (a) the aortic root, coronary arteries and the left ventricle; (b) aortic root and coronary arteries at constant ventricular pressure; and (c) the left ventricle with mean (although not pulse) aortic pressure constant. Electrophysiological recordings were made from slips dissected from the vagus nerve which responded with an increase in discharge to either combined increases in the pressures, or to aortic root injections of veratridine. 3. Recordings were made from twenty‐one vagal afferents. On the basis of their conduction velocities, eleven were classified as non‐myelinated and ten as myelinated. 4. Three non‐myelinated afferents responded to veratridine injections only, three to both veratridine and combined aortic root and ventricular pressure changes, and five to pressure changes only. Responses to pressure occurred only when ventricular systolic pressure exceeded 30 kPa. 5. None of the myelinated afferents responded to veratridine. All showed increases in discharge to combined increases in mean aortic root, coronary arterial and left ventricular systolic pressures, which would be graded over a range similar to that which caused reflex changes. All were more sensitive to changes in mean coronary pressure than to changes in ventricular systolic pressure. 6. We conclude that myelinated vagal afferent nerve fibres, which respond predominantly to changes in mean coronary arterial pressure, are likely to be responsible for the vasodilation to the changes in mean aortic root pressure previously reported. These fibres are probably attached to coronary arterial mechanoreceptors.
Properties of afferent nerve fibres supplying the saphenous vein in the cat.
Authors: Michaelis M , Göder R , Häbler H J , Jänig W
Published: December 2014

1. We examined the responses of primary afferent neurones supplying a vascularly isolated segment of the saphenous vein to mechanical and chemical stimuli in anaesthetized cats. Activity was recorded from centrally cut axons of afferent nerve fibres which were isolated from the saphenous nerve near its junction with the femoral nerve. 2. A total of thirty units responded to one of these stimuli and twenty‐three of them were activated by local mechanical stimulation of the venous wall. Most receptive fields were circular spots. The response of the isolated venous segment to distension was tested in fifteen out of thirty units and eight out of fifteen were activated. Intravasal threshold pressures inducing discharges were in the range of 35‐250 mmHg with a mean of 120 mmHg. 3. Twenty‐seven out of the thirty units were tested for both mechano‐ and chemosensitivity. Thirteen were classified as A fibres and fourteen as C fibres with conduction velocities of 5‐30 m s‐1 and less than 2.5 m s‐1 respectively. Twenty fibres (12/13 A, 8/14 C) were mechanosensitive. Two‐thirds of the mechanosensitive A (8/12) and all of the mechanosensitive C fibres (8/8) responded to at least one of the chemical stimuli used: hypertonic saline, bradykinin (BK) or capsaicin. 4. The remaining seven units (6 C, 1 A) were activated by injection of BK into the isolated venous segment but failed to respond to mechanical stimuli. Six were found during five experiments in which BK was used as a search stimulus. Injection of bradykinin into the isolated venous segment repeatedly induced an increase in systemic blood pressure. 5. The proportion of unmyelinated fibres responding to mechanical stimulation of the venous segment was systematically examined in three experiments and amounted to about 1% of the unmyelinated afferents in the saphenous nerve. 6. In conclusion, a small proportion of afferent nerve fibres in the saphenous nerve responds to presumably noxious mechanical and/or chemical stimuli applied to the saphenous vein. These fibres, together with some chemospecific venous afferents, may be capable of encoding nociceptive information from the vein especially under pathological conditions.
Local control of excitation‐contraction coupling in rat heart cells.
Authors: Wier W G , Egan T M , López‐López J R , Balke C W
Published: December 2014

1. Cytosolic free calcium ion concentration ([Ca2+]i) and whole‐cell L‐type Ca2+ channel currents were measured during excitation‐contraction (E‐C) coupling in single voltage‐clamped rat cardiac ventricular cells. The measurements were used to compute the total cellular efflux of calcium ions through sarcoplasmic reticulum (SR) Ca2+ release channels (FSR,rel) and the influx of Ca2+ via L‐type Ca2+ channels (FICa). 2. FSR,rel was elicited by depolarizing voltage‐clamp pulses 200 ms in duration to membrane potentials from ‐30 to +80 mV. Over this range, peak FSR,rel had a bell‐shaped dependence on clamp pulse potential. In all cells, the ‘gain’ of the system, measured as the ratio, FSR,rel(max)/FICa(max), declined from about 16, at 0 mV, to much lower values as clamp pulse voltage was made progressively more positive. We named this phenomenon of change in gain as a function of membrane potential, ‘variable gain’. At clamp pulse potentials in the range ‐30 to 0 mV, the gain differed from cell to cell, being constant at about 16 in some cells, but decreasing from high values (approximately 65) at ‐20 mV in others. 3. At clamp pulse potentials at which Ca2+ influx (FICa) was maintained, FSR,rel also had a small maintained component. When macroscopic Ca2+ influx was brief (1‐2 ms, during ‘tails’ of FICa), FSR,rel rose rapidly to a peak after repolarization and then declined with a half‐time of about 9 ms (typically). 4. The rising phase of [Ca2+]i transients could be interrupted by stopping Ca2+ influx rapidly (by voltage clamp). We therefore termed this phenomenon ‘interrupted SR Ca2+ release’.(ABSTRACT TRUNCATED AT 250 WORDS)
Voltage‐dependent potassium channels in activated rat microglia.
Authors: Nörenberg W , Gebicke‐Haerter P J , Illes P
Published: December 2014

1. Voltage‐dependent currents of untreated (proliferating) and lipopolysaccharide (LPS)‐treated rat microglial cells in culture were recorded using the whole‐cell patch‐clamp technique. 2. Membrane potentials showed prominent peaks at ‐35 mV and ‐70 mV. Membrane potentials of LPS‐treated cells alternated between the two values. This may be due to a negative slope region of the I‐V relation resulting in two zero current potentials. 3. From a holding potential of ‐70 mV, hyperpolarizing steps evoked an inwardly rectifying current both in proliferating and in LPS‐treated cells, while depolarizing steps below ‐50 mV evoked an outwardly rectifying current only in LPS‐treated microglia. The currents were K+ selective, as indicated by their reversal potential of approximately 0 mV in symmetric K+ concentrations (150 mM both intra‐ and extracellularly) and the reversal potential of the outward tail currents of approximately ‐90 mV at a normal extracellular K+ concentration (4.5 mM). 4. The activation of the outward current could be fitted by Hodgkin‐Huxley‐type n4 kinetics. The time constant of activation depended on voltage. 5. The inactivation of the inward and outward currents could be fitted by a single exponential. The time constant of the inward current inactivation was dependent on voltage, whereas the time constant of the outward current inactivation was virtually independent of voltage, except near the threshold of activation. Recovery of the outward from inactivation was slow and could be fitted by two exponentials. Responses to depolarizing steps were stable at 0.125 Hz, but greatly decreased from the first to the second pulse at 1 Hz. 6. The inactivation of the inward, but not of the outward, current disappeared in a low Na(+)‐containing medium (5 mM). The inward current was selectively inhibited by extracellular Cs+ and Ba2+. The outward current was selectively inhibited by Cd2+, 4‐aminopyridine and charybdotoxin. Replacement of intracellular K+ by an equimolar concentration of Cs+, and the extracellular application of tetraethylammonium and quinine inhibited both currents. 7. An increase of extracellular Ca2+ from 2 to 20 mM resulted in outwardly rectifying K+ channels activating at more positive potentials. Omission of Ca2+ from the extracellular medium had the opposite effect. When the intracellular free Ca2+ was increased from 0.01 to 1 microM, the outward current amplitudes were depressed. The Ca2+ ionophore A23187 had a similar effect. 8. LPS‐treated microglial cells possess inwardly and outwardly rectifying K+ channels. The physiological and pharmacological characteristics of these two channel populations are markedly different.(ABSTRACT TRUNCATED AT 400 WORDS)
Melanostatin (NPY) inhibited electrical activity in frog melanotrophs through modulation of K+, Na+ and Ca2+ currents.
Authors: Valentijn J A , Vaudry H , Kloas W , Cazin L
Published: December 2014

1. Melanostatin, a thirty‐six amino acid peptide recently isolated from the frog brain due to its ability to inhibit alpha‐melanocyte‐stimulating hormone (alpha‐MSH) release, is the amphibian counterpart of mammalian neuropeptide Y (NPY). The effect of synthetic melanostatin on the bioelectrical activity of cultured frog melanotrophs was studied in 124 cells by using the whole‐cell patch‐clamp technique. 2. In current‐clamp experiments, melanostatin (1 microM) provoked a reversible hyperpolarization and a suppression of spontaneous action potentials. In some cells the hyperpolarizing response was absent, but an arrest of spike firing still occurred. 3. Melanostatin‐induced hyperpolarization was associated with a decrease in membrane resistance. In voltage‐clamp experiments, melanostatin induced an outward current at a constant command potential. This hyperpolarizing outward current appeared to be carried by potassium ions. 4. Cell dialysis with the non‐hydrolysable GTP analogue guanosine‐5'‐O‐(3‐thiotriphosphate) (GTP gamma S) sustained the outward current produced by melanostatin. Dopamine (1 microM), which generates a similar hyperpolarizing outward current in frog melanotrophs, was not capable of increasing the current provoked by melanostatin and sustained by GTP gamma S. 5. Melanostatin also modulated voltage‐operated currents. The amplitude of voltage‐activated potassium current was increased by 30%. 6. Melanostatin reduced the fast sodium current. This inhibitory effect was rather persistent compared to the other modulated currents. 7. Melanostatin markedly scaled down high voltage‐activated N‐ and L‐like calcium currents. The activation kinetics of these two calcium currents were not altered by the peptide. 8. Pretreatment of melanotrophs with pertussis toxin (1 microgram ml‐1) blocked melanostatin‐induced inhibition of N‐ and L‐like calcium currents. 9. It is concluded that the NPY‐related peptide melanostatin generates a very complex pattern of electrical responses in frog melanotrophs, including hyperpolarization and modulation of voltage‐activated currents underlying action potentials. G proteins appear to mediate at least part of these effects.
Reflex recruitment of medullary gasping mechanisms in eupnoea by pharyngeal stimulation in cats.
Authors: Fung M L , St John W M , Tomori Z
Published: December 2014

1. Mechanical stimulation of the naso‐ and oropharynx causes the replacement of the eupnoeic ventilatory pattern by a brief, but large, burst of activity of the phrenic nerve. Our purpose was to define whether these changes in phrenic activity represent a switch to gasping. 2. In decerebrate, vagotomized, paralysed and ventilated cats, mechanical stimulation of the pharynx was performed during eupnoea, apneusis and gasping. The latter two ventilatory patterns were produced by ventilating the experimental animal with 1.0% carbon monoxide in air or with 100% nitrogen. Eupnoea could be re‐established by a recommencement of ventilation with oxygen. 3. The rate of rise of phrenic activity and its peak height were much greater following mechanical stimulation of the pharynx than the phrenic bursts of eupnoea or apneusis. The durations of phrenic burst and the period between these were much less following pharyngeal stimulation. In contrast, these variables of phrenic activity were the same during pharyngeal stimulation and in gasping. 4. Previous studies had established that activity within a region of the lateral tegmental field of medulla is critical for the manifestation of gasping. Hence, electrical stimulation of this region during gasping elicits premature gasps whereas its ablation irreversibly eliminates gasping. 5. We positioned a multibarrelled pipette in the critical medullary region for gasping. Its location was verified, once gasping was established in hypoxia or anoxia, by the elicitation of premature gasps following electrical stimulation. Neurons in this region were destroyed by microinjections of the neurotoxin kainic acid; in a few experiments the region was destroyed by electrolytic lesions. 6. Following destruction of the region of the lateral tegmental field, gasping could no longer be provoked in anoxia. In contrast, the eupnoeic pattern of phrenic activity continued. However, mechanical stimulation of the pharynx no longer caused any changes in the on‐going pattern of phrenic activity. 7. We conclude that mechanical stimulation of the pharynx elicits a powerful reflex by which eupnoea is suppressed and gasping is elicited. Stated differently, the changes in phrenic activity during this pharyngeal stimulation in fact represent gasps. 8. Gasps are dependent upon activity within a region of the lateral tegmental field of the medulla. This region plays no role in the neurogenesis of eupnoea. Hence, our results provide additional support for the concept that there are multiple sites for ventilatory neurogenesis in the mammalian brainstem.
Starling pressures in the human arm and their alteration in postmastectomy oedema.
Authors: Bates D O , Levick J R , Mortimer P S
Published: December 2014

1. Surgery and radiotherapy to axillary lymph nodes during breast cancer treatment is often followed, commonly years later, by chronic postmastectomy oedema (PMO). PMO is considered a ‘high protein’ oedema due to reduced axillary lymph drainage. Since oedema formation also depends on fluid input (capillary filtration), we studied the Starling pressures in the affected and contralateral arm. Colloid osmotic pressure was measured in patient serum (pi p) and interstitial fluid (pi i). Subcutis fluid was collected from PMO arms by both wick and aspiration methods, and from the control arm by the wick method only. Interstitial hydraulic pressure (P(i)) was measured by the wick‐in‐needle method. 2. Oedema pi i was 19.2 +/‐ 4.1 cmH2O (n = 13, wick) to 16.3 +/‐ 4.4 cmH2O (n = 41, aspirate; difference not significant; mean +/‐ S.D. throughout). This was significantly lower than pi i in the control arm (21.4 +/‐ 3.8 cmH2O, n = 14, P < 0.01, analysis of variance). Also, there was a negative correlation between oedema pi i and the percentage increase in arm volume (correlation coefficient r = ‐0.35, P < 0.05) in contrast to conventional expectation. 3. Oedema P(i) (1.9 +/‐ 2.0 cmH2O, n = 28) exceeded the subatmospheric control P(i) (‐2.8 +/‐ 3.0 cmH2O; P < 0.01). Venous and arterial pressures were normal but pi p was subnormal (31.1 +/‐ 2.7 cmH2O, n = 47). 4. Net pressure opposing capillary blood pressure, P(o), was calculated as P(i) + sigma (pi p‐pi i) for a reflection coefficient, sigma, of 0.90‐0.99.(ABSTRACT TRUNCATED AT 250 WORDS)
Cation‐dependent gating of the hyperpolarization‐activated cation current in the rabbit sino‐atrial node cells.
Authors: Maruoka F , Nakashima Y , Takano M , Ono K , Noma A
Published: December 2014

1. The gating properties of the hyperpolarization‐activated cation current (I(f) or Ih) were investigated in single pacemaker cells dissociated from the rabbit sino‐atrial node. 2. The whole‐cell I(f) was recorded in the presence of different external cations. The inward I(f) was increased when external Na+ was replaced with K+, and was decreased in Li+ or Rb+ solution. In Tris+ and Cs+ solutions, the inward I(f) was negligible. The outward tail current recorded upon depolarization was largest in Li+ solution and smaller in a sequence of Na+, Tris+ and K+ solutions. In Rb+ and Cs+ solutions, only a small tail current was recorded. 3. The outward tail current had a ‘shoulder’ in Na+ solution, which was much delayed by replacing Na+ with Li+. In K+ solution, the decay of the tail current was much faster, and no obvious shoulder was recorded. The tail current was slowest in Li(+)‐rich and 0 mM K+ solution, and was progressively accelerated by adding K+ over the range from 0 to 3 mM. The tail current at 30 mM [K+]o showed only a small shoulder. A common binding site to modulate the I(f) deactivation was suggested for monovalent cations. 4. The shoulder of the I(f) tail became more evident as I(f) was activated to a larger extent either by prolonging the duration or by increasing the amplitude of the preceding hyperpolarization in both Na+ and Li+ solutions. 5. The I(f) was first activated by hyperpolarizing the membrane to ‐110 mV, and then deactivated by depolarization. The inward tail current at ‐50 mV showed a single exponential decay. At more positive potentials, the shoulder of the outward tail currents became more evident and the rate of the final decay was increased. 6. The time course of I(f) activation was well fitted with the sum of two exponential functions. Time constants of both components were not affected by the external cation (Na+, K+ or Li+) replacement. Likewise, the quasi‐steady state activation was conserved when external Na+ was replaced with Li+. 7. Two closed and three open states were assumed in a sequential state model of the I(f) channel. The cation effects were well simulated by assuming that the deactivation rate was selectively modulated. The flow of I(f) during the spontaneous action potential was calculated. The activation of I(f) started on repolarization to the maximum diastolic potential and reached a maximum in the middle of the diastolic period. Its peak amplitude was 14% of the net inward current during the diastolic period.
Rapid regulation of rat jejunal glucose transport by insulin in a luminally and vascularly perfused preparation.
Authors: Pennington A M , Corpe C P , Kellett G L
Published: December 2014

1. The regulation of glucose transport by physiological concentrations of insulin was investigated using a preparation of rat jejunum perfused in situ with 5 mM glucose on both sides. 2. Luminal uptake was 87% inhibited (P < 0.001) by 0.2 mM phlorizin, indicating that it occurred by means of the Na(+)‐D‐glucose cotransporter. Vascular uptake was completely abolished by 0.2 mM phloretin, indicating that it was facilitated in nature. 3. When infused into the vascular circuit, insulin (10(‐11) to 10(‐7) M) stimulated vascular, and inhibited luminal, glucose uptake to a similar extent. Maximal stimulation of vascular uptake was increased by 40% compared with control infusions (P < 0.01) and occurred at 10(‐10) M insulin. These effects were independent of changes in metabolism and vascular glucose concentration. 4. The time taken for half‐maximal stimulation of vascular uptake was 6.3 +/‐ 0.7 min and preceded that for inhibition of luminal uptake by 6.5 +/‐ 1.3 min (P < 0.02). 5. The rapid inhibition of luminal glucose uptake by the acute administration of insulin was also detected by perfusion of jejunal loops in vivo. 6. It is concluded that the transport steps involved in intestinal glucose uptake are subject to rapid regulation by physiological concentrations of insulin and that the initial site of action is on the vascular side.