bluuebunny/crossref_metadata_2025 huggingface dataset:
Bradykinin‐induced modulation of the response behaviour of different types of feline group III and IV muscle receptors.
Authors: Mense S , Meyer H
Published: December 2014

1. In order to test the hypothesis that bradykinin has a sensitizing action on muscle receptors (e.g. during a myositis), the response properties of single group III and IV afferent units from the cat gastrocnemius‐soleus muscle were compared before and after infiltration of their receptive fields with a bradykinin solution. According to their responses to graded natural stimuli (local pressure, stretch, contractions and temperature changes) the units were classified as (a) nociceptors, (b) low‐threshold pressure‐sensitive (LTP) receptors, (c) contraction‐sensitive (CS) receptors and (d) thermosensitive receptors. 2. Bradykinin activated the majority of both the nociceptive and low‐threshold (LTP, CS and thermosensitive) receptors but a sensitization was prominent only among the nociceptors. Most of the sensitized nociceptors showed increased responses to mechanical, but not to thermal, stimuli. The sensitization appeared to be quite specific in that the nociceptors were sensitized either towards local pressure stimulation or to active contractions, but never towards both forms of stimulation. 3. Both group III and group IV nociceptors were sensitized by bradykinin, the proportion of sensitized receptors being greater for group III units. 4. Some of the low‐threshold receptors (particularly the CS units) showed a desensitization under the influence of bradykinin. 5. Although bradykinin (by lowering the mechanical thresholds of nociceptors into the innocuous range) could produce the symptom of allodynia, it was not capable of eliciting all the changes in receptor behaviour which are known to occur in inflamed tissues. For instance, no ongoing activity of longer duration and no substantial sensitization of low‐threshold receptors have been observed in the present study.
Voltage sensors of the frog skeletal muscle membrane require calcium to function in excitation‐contraction coupling.
Authors: Brum G , Fitts R , Pizarro G , Ríos E
Published: December 2014

1. Intramembrane charge movements and changes in intracellular Ca2+ concentration (Ca2+ transients) elicited by pulse depolarization were measured in frog fast twitch cut muscle fibres under voltage clamp. 2. Extracellular solutions with very low [Ca2+] and 2 mM‐Mg2+ , shown in the previous paper to reduce Ca2+ release from the sarcoplasmic reticulum (SR), were found to cause two changes in charge movement: (a) a decrease (‐12 nC/microF) in the charge that moves during depolarizing pulses from ‐90 to 0 mV, termed here 'charge 1'; (b) an increase (+7 nC/microF) in the charge moved by hyperpolarizing pulses from ‐90 to ‐180 mV, termed 'charge 2'. 3. The increase in charge moved by hyperpolarizing pulses was correlated (r = 0.64) with the decrease in charge moved by depolarizing pulses and both were correlated with the inhibition of Ca2+ release recorded in the same fibres. 4. The low Ca2+ solutions caused a shift to more negative voltages of the dependence relating charge movement and holding potential (VH). This shift is of similar magnitude (about 22 mV) and direction as the shift in the curve relating Ca2+ release flux to VH (previous paper). 5. In solutions with normal [Ca2+] a conditioning depolarization to 0 mV, of 2 s duration, placed 100 ms before a test pulse from ‐70 to 0 mV, reduced by 30% the amount of charge displaced by the test pulse. Conditioning pulses of 1 s or less caused potentiation of charge movement by up to 30%. 6. In low Ca2+ solutions, reduction of charge was observed at all durations of the conditioning pulse. The duration for half‐inhibition was near 200 ms. 7. An extracellular solution with no metal cations caused a more radical inhibition than the low Ca2+ solutions that contained Mg2+. The inhibition of Ca2+ release was essentially complete (90‐100%). The charge moved by a pulse to 0 mV was reduced by 20 nC/microF and the charge moved by a pulse to ‐170 mV increased 8 nC/microF. This shows that Mg2+ supports excitation‐contraction (E‐C) coupling to some extent. 8. A state model of the voltage sensor of E‐C coupling explains qualitatively the observations in both papers.(ABSTRACT TRUNCATED AT 400 WORDS)
Secretion of corticotrophin releasing factor from the adrenal during splanchnic nerve stimulation in conscious calves.
Authors: Edwards A V , Jones C T
Published: December 2014

1. The output of corticotrophin releasing factor‐like immunoreactivity (CRF) from the adrenal gland has been investigated using the 'adrenal clamp' technique in conscious calves. 2. Stimulation of the peripheral end of the splanchnic nerve for 10 min increased the mean output of CRF progressively, so that it had risen by about twentyfold, to a peak incremental value of 24 +/‐ 4 pmol min‐1 kg‐1 at 10 min. This response was significantly increased by stimulating in bursts at 40 Hz for 1 s at 10 s intervals, which raised the mean CRF output by 44 +/‐ 7 pmol min‐1 kg‐1 at 10 min (P less than 0.05). 3. The mean output of adrenaline and noradrenaline rose more abruptly in response to splanchnic nerve stimulation with peak incremental values realized within 2.5 min. However, the ratios of adrenal CRF to catecholamine output were closely similar during the later stages of stimulation (7.5‐10 min). There was a similarly abrupt rise in adrenal cortisol output in response to splanchnic nerve stimulation which was, nevertheless, linearly related to arterial plasma ACTH concentration throughout. 4. In hypophysectomized calves, administration of adrenocorticotrophic hormone (ACTH1‐24) at a dose of 5 ng min‐1 kg‐1 reduced the output of adrenal CRF in response to splanchnic nerve stimulation by about 50% (P less than 0.05). 5. CRF isolated from adrenal venous effluent plasma, collected both at rest and during splanchnic nerve stimulation, was separated by reverse‐phase high‐pressure liquid chromatography and found to elute in a position identical to that of human 41CRF. This suggests that adrenal CRF is structurally closely similar to its pituitary counterpart.
Properties of single potassium channels modulated by glucose in rat pancreatic beta‐cells.
Authors: Ashcroft F M , Ashcroft S J , Harrison D E
Published: December 2014

1. The patch clamp method has been used to examine the effect of glucose on single K+ channel currents recorded from cell‐attached patches on dissociated rat pancreatic beta‐cells. Patch pipettes contained a 140 mM‐K+ solution. 2. In glucose‐free solution three types of K+ channels were observed. Two of these, having conductances of around 50 pS (G‐channel) and 20 pS when the external K+ concentration, [K+]0, was 140 mM, were active at the resting potential of the cell. The G‐channel was observed in more patches and showed higher activity; it therefore appears to contribute the major fraction of the resting K+ permeability of the beta‐cell. At membrane potentials positive to about +20 mV a third type of K+ channel, having a mean conductance of 120 pS, was activated. The open probability of this channel was strongly voltage dependent and increased with depolarization. 3. The reversal potential of the G‐channel current was shifted 59 mV by a 10‐fold change in external K+ (Na+ substitution) indicating the channel is highly K+ selective. The single‐channel conductance varied with [K+]o as predicted from the Goldman‐Hodgkin‐Katz equation; at physiological [K+]o (5 mM‐K+) an inward conductance of around 10 pS is predicted. The amplitude of the single‐channel current showed a tendency to saturate with increasing [K+]o. 4. Single G‐channel currents show burst kinetics indicating at least two closed states. The open and closed (gap) times within the bursts were distributed exponentially with time constants of 2.5 ms (tau o) and 0.5 ms (tau c1) respectively at the resting potential of the cell. There was little change in tau c1 over the voltage range ‐40 to 60 mV (pipette potential) but tau o increased slightly with membrane depolarization. 5. The addition of glucose to the bath solution produced a reversible, dose‐dependent decrease in G‐channel activity. This decrease results principally from a reduction in the frequency and duration of the bursts of openings with increasing glucose. In addition, the mean open time decreases. The short gaps during the bursts were little affected by glucose. 6. At glucose concentrations of .10 mM and above the decrease in G‐channel activity is accompanied by an increase in the input resistance of the cell and by the initiation of action potentials. 7. It is concluded that glucose metabolism results in a reduction of G‐channel open probability and thereby produces depolarization of the beta‐cell.
Inactivation, reactivation and pacing dependence of calcium current in frog cardiocytes: correlation with current density.
Authors: Argibay J A , Fischmeister R , Hartzell H C
Published: December 2014

1. Ca2+ currents were measured in single cells isolated from frog ventricle using the whole‐cell patch clamp technique and a perfused pipette. K+ currents were blocked with intracellular (120 mM) and extracellular (20 mM) Cs+. 2. A single type of Ca2+ current (ICa) was found in these cells. The current activated at voltages positive to ‐30 mV, exhibited a symmetrical current‐voltage relationship with a peak at 0 mV, and was slowly inactivating with Ba2+ as charge carrier. 3. Large variations in ICa amplitude were observed from cell to cell (ICa at 0 mV = 293.1 +/‐ 283.3 pA; N = 152). These variations were not due simply to differences in cell membrane area, which was estimated by cell membrane capacitance (Cm), because the density of Ca2+ current (dICa = ICa/Cm) also varied significantly from cell to cell (1.3‐28 pA/pF at 0 mV; mean +/‐ S.D. = 4.49 +/‐ 3.96; N = 152). 4. The inactivation curve of ICa was a complex function of membrane potential. 200 ms pre‐pulses to voltages between ‐60 and +20 mV progressively inactivated ICa elicited by a subsequent test pulse with half‐maximal inactivation occurring for pre‐pulses to approximately ‐40 mV. With pre‐pulses positive to +20 mV, ICa elicited by the test pulse became progressively larger. The degree of inactivation induced by a 200 ms depolarization to potentials more positive than +20 mV varied significantly from cell to cell, while no such variations were observed in the negative range of membrane potentials. 5. The time course of reactivation (i.e. removal from inactivation) of ICa at ‐80 mV often exhibited an overshoot. The amplitude of the overshoot varied between 100% (i.e. no overshoot) and approximately 180% in eighty‐one cells. 6. The degree of inactivation at positive potentials (+100 mV) and the amplitude of the overshoot were strongly correlated with the Ca2+ current density. The overshoot was more pronounced, the reactivation was faster, and the inactivation at positive potentials was less in cells with lower ICa density. 7. Increasing the stimulation frequency from 0.125 to 2 Hz induced a positive staircase of ICa in cells with ICa density less than 2 pA/pF and a negative staircase in cells with ICa density greater than 3 pA/pF. 8. Perfusing the patch pipette with 5 mM‐BAPTA instead of EGTA reduced the amplitude of the overshoot and slightly slowed the inactivation kinetics. Replacing extracellular Ca2+ ions by Ba2+ ions completely suppressed the overshoot.(ABSTRACT TRUNCATED AT 400 WORDS)
Evidence for two functionally different membrane fractions in bovine retinal rod outer segments.
Authors: Bauer P J
Published: December 2014

1. Cyclic GMP‐induced and Na+‐induced Ca2+ releases from Ca2+‐containing photoreceptor membrane vesicles were investigated using the Ca2+‐sensitive dye Arsenazo III. Bovine photoreceptor membrane vesicles were prepared by osmotic lysis and hypotonic wash of purified rod outer segments. 2. Calcium was entrapped into these vesicles either by utilizing their passive membrane permeability ('passive' Ca2+ loading), or by activating cyclic GMP‐dependent channels (cyclic GMP‐stimulated Ca2+ loading), or by Na+‐Ca2+ exchange (Na+‐stimulated Ca2+ loading). 3. After passive Ca2+ loading, cyclic GMP released at most about 23% of the total Ca2+ which could be released with the Ca2+ ionophore A23187 (Km = 6.5 +/‐ 0.92 microM (6); Hill coefficient 1.68 +/‐ 0.19 (6]. 4. Millimolar concentrations of Na+ also induce Ca2+ releases from passively Ca2+‐loaded outer segment membrane vesicles of at most 26% of the total releasable Ca2+. 5. For passively Ca2+‐loaded outer segment membrane vesicles, the sum of a partial cyclic GMP‐induced Ca2+ release and a consecutive saturating Na+‐induced Ca2+ release, or vice versa, the sum of a partial Na+‐induced Ca2+ release and a consecutive saturating cyclic GMP‐induced Ca2+ release, was about 25% of the total releasable Ca2+. 6. Both cyclic GMP‐induced and Na+‐induced Ca2+ release was greater than 25%, up to 50% of the total releasable Ca2+ if either cyclic GMP‐stimulated or Na+‐stimulated Ca2+ loading of outer segment membrane vesicles was employed. 7. When the outer segment membrane vesicles were mildly sonicated in a water bath, the maximal percentages of Ca2+ releasable by both cyclic GMP and Na+ dropped, reaching final values, after a 60 s sonication period, of 2.3% for the cyclic GMP‐induced Ca2+ release and 7% for the Na+‐induced Ca2+ release. 8. It is concluded from these results that outer segment membrane vesicles comprise two populations of vesicles, one which contains cyclic GMP‐dependent channels and Na+‐Ca2+ exchanging proteins, and another one which contains neither of these proteins. 9. The sonication experiments are interpreted as suggesting that these two vesicle populations correspond to plasma and disc membranes of the rod outer segments, respectively.
Bistability of alpha‐motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5‐hydroxytryptophan.
Authors: Hounsgaard J , Hultborn H , Jespersen B , Kiehn O
Published: December 2014

1. In the preceding paper (Crone, Hultborn, Kiehn, Mazieres & Wigström, 1988) it was shown that a short‐lasting synaptic excitation (‘on’ stimulus) of extensor motoneurones (primarily triceps surae) in the decerebrate cat often resulted in a maintained excitability increase, which could be reset by a short‐lasting inhibitory stimulus train (‘off’ stimulus). In the present experiments intracellular recording from triceps surae motoneurones and the electroneurogram (ENG activity) from triceps surae nerve branches were performed in parallel. 2. Sustained firing of individual triceps surae motoneurones was most often recorded in parallel with the maintained ENG activity following a synaptic ‘on’ stimulus. When the motoneurone was silenced, by a hyperpolarizing current through the microelectrode, there was no sign of on‐going synaptic excitation during the maintained ENG activity following an ‘on’ stimulus. It was therefore suggested that voltage‐dependent intrinsic properties of the motoneurones themselves could be responsible for the maintained firing. 3. In confirmation of this hypothesis it was found that short‐lasting depolarizing current pulses through the recording microelectrode could trigger a self‐sustained firing in the motoneurone provided that the bias current (i.e. the holding potential) was kept within certain limits. Hyperpolarizing current pulses terminated the firing. When the spike‐generating mechanism was inactivated (by long‐lasting excessive depolarization) similar depolarizing and hyperpolarizing current pulses could initiate and terminate plateau potentials in the motoneurones. By grading the depolarizing current pulses it was found that the plateau potentials were of all‐or‐none character, typically around 10 mV in amplitude. The two levels of excitability which can be triggered by short‐lasting excitation and inhibition of the motoneurones is referred to as ‘bistable’ behaviour of the motoneurones. 4. After an acute spinal transection, in the unanaesthetized cat, the bistable behaviour of the motoneurones disappeared. However, it reappears following intravenous injection of the serotonin precursor 5‐hydroxytryptophan (50‐120 mg/kg). 5. Individual triceps surae motor units were recorded by selective EMG electrodes during tonic stretch reflexes in the decerebrate preparations. Based on an analysis of their firing pattern during lengthening and shortening (or vibration) of the muscle it is suggested that plateau potentials in motoneurones are recruited during the tonic stretch reflex. Furthermore, it is argued that a quantitatively important part of the depolarization of motoneurones during the tonic stretch reflex indeed originates from these plateau potentials.(ABSTRACT TRUNCATED AT 400 WORDS)
The effects of changes in muscle length during diastole on the calcium transient in ferret ventricular muscle.
Authors: Allen D G , Nichols C G , Smith G L
Published: December 2014

1. Ferret papillary muscles were isolated and injected with aequorin to measure intracellular Ca2+ concentration [( Ca2+]i). Developed tension and [Ca2+]i were measured in response to length changes. 2. A maintained reduction in muscle length produced an immediate decrease in developed tension followed by slow decline over 10‐20 min. This slow decline in tension was accompanied by a slow decline in the amplitude of the systolic [Ca2+]i rise (the Ca2+ transient). The immediate decrease in tension was accompanied by a prolongation of the Ca2+ transient and an abbreviation of the twitch. 3. Repeated reductions in muscle length timed to occur only during the period of contraction (systolic shortening) produced an immediate decrease of developed tension but the subsequent slow decline was substantially smaller. The slow decline in the amplitude of the Ca2+ transients was also smaller. The prolongation of the Ca2+ transient and abbreviation of the twitch were similar to those observed with a maintained reduction of length. 4. Repeated reductions in muscle length during the period between contractions (diastolic shortening) did not produce the immediate decrease of tension but the slow decline of tension was present. The slow decline in the amplitude of the Ca2+ transients was also present. However no change in the duration of the Ca2+ transient or the twitch was present under these conditions. 5. These results suggest that diastolic muscle length can influence the amplitude of the Ca2+ transients achieved during systole. This conclusion was confirmed by experiments in which the recovery of tension and Ca2+ transients was observed after periods of rest. Both developed tension and Ca2+ transients on recovery from a rest were reduced when the rest occurred at a short length in comparison with a long length. 6. We suggest that muscle length influences resting [Ca2+]i and this in turn affects the Ca2+ transients and developed tension.
Pacemaker activity in the proximal lower oesophageal sphincter of the dog.
Authors: Huizinga J D , Walton P D
Published: December 2014

1. The electrical and mechanical activities of different regions of the canine lower oesophageal sphincter were measured using the single sucrose gap technique. 2. Spontaneous electrical activity was found in the region 0‐6 mm oral to the squamocolumnar border. 3. The electrical activity consisted of bursts of spikes superimposed on slow waves. The slow‐wave frequency ranged from 0.6 to 5 min‐1 in different muscle strips. 4. The slow wave‐spike complex and associated contraction were insensitive to tetrodotoxin and atropine. 5. In the pacemaker region, electrical stimulation of intrinsic nerves evoked excitatory junction potentials (atropine sensitive), inhibitory junction potentials (non‐adrenergic) and post‐stimulus excitation. 6. Increase in the frequency of the slow waves was obtained by muscarinic receptor stimulation (carbachol 10(‐7) M) and 10 mM‐KCl. 7. The distal lower oesophageal sphincter exhibited a high basal tension but did not show spontaneous electrical activity and stimulation of intrinsic nerves revealed only non‐cholinergic, non‐adrenergic inhibition. 8. The electrical slow‐wave activity observed in the proximal sphincter may constitute the control mechanism for the phasic nature of the contractile activity seen during both the postprandial period and phase III of the interdigestive migrating myoelectric complex. 9. The neural cholinergic activity present in the proximal lower oesophageal sphincter suggests the possibility of neural modulation of the myogenic control activity.
Pertussis toxin inhibits endothelium‐dependent relaxations to certain agonists in porcine coronary arteries.
Authors: Flavahan N A , Shimokawa H , Vanhoutte P M
Published: December 2014

1. Pertussis toxin inactivates Gi‐protein, which mediates the inhibitory effects of receptors on adenylate cyclase. The effects of the toxin on endothelium‐dependent and independent relaxations were determined in porcine coronary arteries. 2. Arterial rings (with and without endothelium) were suspended for isometric tension recording in organ chambers filled with modified Krebs‐Ringer bicarbonate solution (maintained at 37 degrees C, gassed with 95% O2 and 5% CO2). 3. Incubation of the tissues with pertussis toxin (100 ng/ml for 60 min) virtually abolished the endothelium‐dependent relaxations produced by the alpha 2‐adrenergic agonist, UK 14304, and by 5‐hydroxytryptamine. Endothelium‐dependent relaxations to thrombin and to aggregating platelets were markedly reduced, whereas those produced by bradykinin were only minimally affected. Endothelium‐dependent responses produced by the calcium ionophore (A23187) and by adenosine diphosphate were not altered by pertussis toxin. 4. Pertussis toxin did not affect the direct, endothelium‐independent relaxations produced by nitric oxide, or by adenosine diphosphate. 5. These experiments demonstrate that pertussis toxin interferes with the release of endothelium‐derived relaxing factor(s) evoked by certain, but not all, endothelial activators. The release of endothelium‐derived relaxing factor(s) may occur through different pathways involving Gi‐protein‐dependent and independent mechanisms.
Effects of a monoclonal anti‐acetylcholine receptor antibody on the avian end‐plate.
Authors: Maselli R A , Nelson D J , Richman D P
Published: December 2014

1. The effects of anti‐acetylcholine receptor (AChR) monoclonal antibodies (mAbs) 370 and 132A on miniature end‐plate potentials (MEPPs) and end‐plate currents (EPCs) in the posterior latissimus dorsi muscle of adult chickens were investigated. 2. After incubation of the electrophysiological preparation with mAb 370 (5‐50 micrograms/ml), which blocks both agonist (carbamylcholine) and alpha‐bungarotoxin (alpha‐BTX) binding and induces a hyperacute form of experimental autoimmune myasthenia gravis (EAMG), MEPP and EPC amplitudes were irreversibly reduced. 3. This effect was not associated with any significant change in the time constant describing EPC decay (tau EPC), current reversal potential, or the voltage dependence of tau EPC. The tau EPC at ‐80 mV was 5.9 +/‐ 0.6 ms before incubation with mAb 370 (50 micrograms/ml) and 6.0 +/‐ 0.9 ms afterwards. Current reversal potential was ‐3.9 +/‐ 0.4 mV before mAb incubation and ‐4.8 +/‐ 1.5 mV afterwards. The change in membrane potential required to produce an e‐fold change in tau EPC was 128 +/‐ 2.3 mV before antibody incubation compared to 125 +/‐ 6.6 mV after incubation. 4. A second anti‐AChR mAb, 132A (50 micrograms/ml), which is capable of inducing the classically described form of EAMG without blocking agonist or alpha‐BTX binding, or inducing hyperacute EAMG, produced no significant change in MEPP amplitude, EPC amplitude, tau EPC or EPC reversal potentials. 5. The mAb 370 (50 micrograms/ml) induced a partially reversible decrease of the quantal content of the neurally evoked end‐plate potential (EPP). This effect was not observed with mAb 132A, (+)tubocurarine (10(‐7)‐10(‐5) g/ml) or an irrelevant anti‐oestrogen receptor mAb. 6. These data suggest that the rapid onset of weakness observed in chicken hatchlings after the injection of mAb 370 (Gomez & Richman, 1983) can be attributed to a combined effect of a block of acetylcholine (ACh)‐induced ion channel activity in the postsynaptic membrane and a reduction of the neurally evoked release of acetylcholine from the nerve terminal.
Voltage‐dependent and calcium‐dependent inactivation of calcium channel current in identified snail neurones.
Authors: Gutnick M J , Lux H D , Swandulla D , Zucker H
Published: December 2014

1. The dependence of Ca2+ current inactivation on membrane potential and intracellular Ca2+ concentration ([Ca2+]i) was studied in TEA‐loaded, identified Helix neurones which possess a single population of high‐voltage‐activated Ca2+ channels. During prolonged depolarization, the Ca2+ current declined from its peak with two clearly distinct phases. The time course of its decay was readily fitted by a double‐exponential function. 2. In double‐pulse experiments, the relationship between the magnitude of the Ca2+ current and the amount of Ca2+ inactivation was not linear, and considerable inactivation was present, even when conditioning pulses were to levels of depolarization so great that Ca2+ currents were near zero. Similar results were obtained when external Ca2+ was replaced by Ba2+. 3. In double‐pulse experiments, hyperpolarization during the interpulse interval served to reprime a portion of the inactivated Ca2+ current for subsequent activation. The extent of repriming increased with hyperpolarization, reaching a maximum between ‐130 and ‐150 mV. The effectiveness of repriming hyperpolarizations was considerably increased when Ca2+ was replaced by Ba2+. 4. A significant fraction of inactivated Ca2+ channels can be recovered during hyperpolarizing pulses lasting only milliseconds. If hyperpolarizing pulses were applied before substantial inactivation of Ca2+ current, Ca2+ channels remained available for activation despite considerable Ca2+ entry. 5. The relationship between [Ca2+]i and inactivation was investigated by quantitatively injecting Ca2+‐buffered solutions into the cells. The time course of Ca2+ current inactivation was unchanged at free [Ca2+] between 1 x 10(‐7) and 1 x 10(‐5) M. From 1 x 10(‐7) to 1 x 10(‐9) M, inactivation became progressively slower, mainly due to a decrease of the amplitude ratio (fast/slow) of the two components of inactivation, which fell from about unity to near zero at 1 x 10(‐9) M. In double‐pulse experiments, recovery from inactivation was enhanced in neurones that had been injected with Ca2+ chelator. 6. We conclude that inactivation of Ca2+ channels in these neurones depends on both [Ca2+]i and membrane potential. The voltage‐dependent process may serve as a mechanism to quickly recover inactivated Ca2+ channels during repetitive firing despite considerable Ca2+ influx. 7. The results are discussed in the framework of a model which is based on two states of inactivation, INV and INCA, which represent different conformations of the inactivating substrate, and which are both reached from a lumped state of activation (A). Inactivation leads to high occupancy of INV during depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
Local inhibition of converting enzyme and vascular responses to angiotensin and bradykinin in the human forearm.
Authors: Benjamin N , Cockcroft J R , Collier J G , Dollery C T , Ritter J M , Webb D J
Published: December 2014

1. The function of angiotensin converting enzyme was investigated in twenty‐four healthy men. Forearm blood flow was measured under basal conditions and during administration of enalaprilat (a converting enzyme inhibitor) and/or peptide substrates of converting enzyme into the left brachial artery. Blood flow was compared in the two arms. 2. Enalaprilat had no effect on basal blood flow. The concentration of enalaprilat in venous blood from the control arm was low, and plasma renin activity was not increased, indicating that systemic inhibition of converting enzyme did not occur. 3. Effects of angiotensin and of bradykinin, administered intra‐arterially, were limited to the infused arm. Enalaprilat (13 nmol min‐1) inhibited converting enzyme in the infused arm, in which it caused approximately a 100‐fold reduction in sensitivity to angiotensin I, while having no effect on the vasoconstriction caused by angiotensin II. Enalaprilat increased vasodilatation caused by bradykinin. 4. Aspirin, an inhibitor of cyclo‐oxygenase, did not inhibit vasodilatation caused by bradykinin whether infused alone or with enalaprilat, indicating that these responses are not mediated by prostaglandins. 5. We conclude that under basal conditions neither conversion of angiotensin I to angiotensin II nor degradation of bradykinin determines resistance vessel tone in the human forearm. Converting enzyme may affect vascular tone in situations in which intravascular concentrations of peptides are increased over those present under basal conditions.
The effect of stimulation of the atrial receptors on plasma cortisol level in the dog.
Authors: Drinkhill M J , Mary D A
Published: December 2014

1. Experiments were performed in dogs anaesthetized with alpha‐chloralose to determine whether stimulation of atrial receptors reflexly results in a consistent change in plasma cortisol levels. Either a large balloon in the lumen of the left atrium or small balloons positioned at the upper and middle pulmonary vein‐atrial junctions and atrial appendage were distended. Plasma samples obtained from these dogs during control periods and during periods of stimulation were assayed for plasma cortisol level. 2. Initially, stimulation of left atrial receptors by either large or small balloon distension was shown consistently to cause the responses of an increase in urine flow and a decrease in plasma cortisol level. The responses were greater during stimulation using the large balloon than the small balloons. 3. The afferent limb of the responses was shown to involve the vagal nerves. Cooling of the cervical vagosympathetic nerve trunks to 9 degrees C abolished the responses to balloon distension of an increase in urine flow and decrease in the level of plasma cortisol. 4. The efferent limb of the cortisol response was shown to require the pituitary gland. Hypophysectomy abolished the response of a decrease in plasma cortisol level, but not the diuretic response. 5. It was shown that stimulation of left atrial receptors causes a reflex decrease in plasma cortisol level, the afferent limb of which involved vagal nerves and the efferent limb of which depended on the pituitary gland.
The influence of changes in discharge frequency of corticospinal neurones on hand muscles in the monkey.
Authors: Lemon R N , Mantel G W
Published: December 2014

1. The possibility that the discharge pattern of monkey corticomotoneuronal cells influences the degree to which they facilitate their target hand muscles was tested by compiling spike‐triggered averages of EMG recorded from these muscles. 2. Records were made from area 4 corticomotoneuronal cells in three conscious macaque monkeys while they performed a precision grip between index finger and thumb. Simultaneous EMG recordings were made from up to six different intrinsic hand muscles. Twenty cells which produced clear post‐spike facilitation of one or more muscles were selected for further analysis. 3. Spikes recorded from these cells were grouped according to the occurrence of a previous spike in the periods 0‐10 ms, 10‐20 ms, and so on up to 60‐70 ms before the trigger spike. The post‐spike period in which no additional spikes were allowed to fall was kept at either 12.5 or 25 ms. 4. Spikes selected in this way produced a transient facilitation of their target muscle EMG activity. The peak amplitude of this facilitation was normalized as a percentage of modulation of the background EMG level. The background level was determined from a period in the average to which the cell could not have contributed, because of the post‐trigger spike interval. We verified that the percentage of modulation was not influenced by the overall level of EMG activity, since, for a given interval, the modulation was the same whether the relevant spikes were selected during periods of high‐ or low‐level EMG activity. 5. The relative amplitude of the post‐spike facilitation (i.e. the percentage of modulation) showed marked variation with interspike interval. A full analysis was completed for seventeen neurones. Spikes with the shortest intervals (less than 10 ms) usually produced the strongest effects, and evidence is presented that this was due to temporal summation and facilitation at the corticomotoneuronal synapse. Mid‐range intervals (10‐40 ms) were generally far less effective, although they constituted the highest proportion of cell activity. 6. A striking finding was the strong facilitation generated by the longer interspike intervals (40‐70 ms). Although the absolute size of this post‐spike effect was much smaller than that of the shortest intervals, its percentage of modulation was similar. It is suggested that this enhanced facilitation results from a combination of lower frequency discharge among the active motoneurones, and increased synchrony in the corticomotoneuronal input to them. 7. All of the above results were confirmed by examining cross‐correlations between single corticomotoneuronal cells and single motor units in their target muscle.(ABSTRACT TRUNCATED AT 400 WORDS)
Amplitude and phase of responses of macaque retinal ganglion cells to flickering stimuli.
Authors: Lee B B , Martin P R , Valberg A
Published: December 2014

1. We have measured responses of macaque retinal ganglion cells to a uniform flickering field, with variation in luminance, chromaticity or both (heterochromatic flicker). 2. With heterochromatic flicker, as the luminance ratio of the flicker components was varied, phasic ganglion cell activity went through a minimum and an abrupt phase change close to equal luminance. Tonic ganglion cell responses underwent a gradual phase change without any minimum close to equal luminance. For red on‐centre cells, when wavelengths above 570 nm were altered with white, a progressive phase advance occurred as luminance ratio (L lambda/LW) was increased. With wavelengths below 570 nm a progressive phase lag occurred. For green on‐centre cells, the opposite pattern was found. For all tonic cells, the higher the temporal frequency, the more rapidly did such phase changes occur. A simple model incorporating a centre‐surround delay of 3‐8 ms could quantitatively account for these changes. 3. With luminance flicker of different dominant wavelengths, amplitudes and phase of responses of phasic ganglion cells were independent of wavelength at all frequencies. The amplitude and phase of the responses of tonic ganglion cells was very dependent on wavelength, as well as on flicker frequency. Their characteristics hardly ever resembled results from phasic cells. 4. For achromatic flicker, response phase of tonic cells at or above 10 Hz was variable, probably due to the centre‐surround delay. Such variability was not seen among phasic cells. 5. An interesting implication of these results is that the ability of tonic ganglion cells to unambiguously signal rapid chromatic or spatial change is limited.
Characteristics of synaptic input to three classes of sympathetic neurone in the coeliac ganglion of the guinea‐pig.
Authors: McLachlan E M , Meckler R L
Published: December 2014

1. Intracellular recordings from sympathetic neurones in the isolated coeliac ganglion of guinea‐pigs have been used to define the synaptic input to three subtypes of neurone, classified on the basis of their discharge during maintained depolarizing current as phasic neurones, neurones with prolonged after‐hyperpolarizations (LAH), and tonic neurones. 2. The three classes of neurone were distributed characteristically in different parts of the ganglion. 3. Passive membrane properties differed between the three neurone types. Mean input resistance was highest in phasic neurones and was inversely related to the size of the prolonged calcium‐activated potassium conductance in LAH neurones. Mean input time constant was highest in tonic neurones, because of significantly higher cell capacitance. 4. Phasic and LAH neurones usually received one suprathreshold ('strong') as well as several subthreshold excitatory synaptic potentials (ESPs) from the ipsilateral splanchnic nerve. In general, the amplitude and number of splanchnic inputs were greater, and the occurrence of two strong inputs more common, in phasic than in LAH neurones. The input to tonic neurones was small and usually subthreshold, even with supramaximal splanchnic stimulation. In a few (mostly tonic) neurones lying close to the midline, small ESPs were evoked by contralateral splanchnic stimulation. 5. Antidromic action potentials were evoked in more than half of all neurones by high voltage coeliac nerve stimulation. In addition, multiple small subthreshold ESPs were recorded in virtually all tonic neurones (99%) on coeliac nerve stimulation. In contrast, coeliac stimulation rarely evoked a few very small ESPs in LAH neurones (9%), but no synaptic response in phasic neurones. 6. In about half of the tonic neurones tested (but no phasic or LAH neurones), small ESPs were evoked by stimulation of the intermesenteric nerve. 7. Slow depolarization elicited by repetitive activation of splanchnic and coeliac nerve trunks, at voltages supramaximal for the fast cholinergic responses, were recorded from about half of both phasic and tonic neurones, but only one of twenty‐four LAH neurones. These responses commonly faded during subsequent trials, so that it was difficult to characterize them. 8. The data indicate that the three broad groups of coeliac neurone, classified on the basis of their voltage‐ and calcium‐dependent potassium conductances, receive different patterns of synaptic input. The differences may be related to the three major functions of vasoconstriction, motility and mucosal secretion in the small intestine.
Alterations in [Ca2+]i mediated by sodium‐calcium exchange in smooth muscle cells isolated from the guinea‐pig ureter.
Authors: Aaronson P I , Benham C D
Published: December 2014

1. Sodium‐calcium exchange was studied in single enzymatically isolated cells of the guinea‐pig ureter using the Ca2(+)‐sensitive fluorescent dye Indo‐1 to monitor the intracellular Ca2+ concentration ([Ca2+]i). Patch pipettes containing Indo‐1 were used to introduce the dye into cells, to set the intracellular Na+ concentration ([Na+]i) and control the membrane potential during experiments. 2. With [Na+]i set at 11‐12 mM and a membrane potential of ‐60 or ‐70 mV, brief depolarization of ureter cells elicited typical voltage‐gated inward currents associated with rapid increases in [Ca2+]i which showed a bell‐shaped potential dependence. If Ca2+ currents were blocked with nifedipine, depolarization led to slower rises in [Ca2+]i. The rates and amplitudes of these increased monotonically with progressively larger depolarizations up to +120 mV. 3. The nifedipine‐resistant rises in [Ca2+]i elicited by depolarization were potentiated when the extracellular sodium concentration ([Na+]o) was reduced. Basal levels of [Ca2+]i also increased as [Na+]o was reduced, although the dependence of this effect on [Na+]o was smaller than would be predicted if [Ca2+]i was set only by a Na(+)‐Ca2+ exchange process. 4. The nifedipine‐insensitive rises in [Ca2+]i elicited by depolarization were potentiated at higher basal levels of [Ca2+]i. 5. The ability of cells to reduce [Ca2+]i rapidly following Ca2+ loading during voltage‐gated transients was markedly inhibited if the Na+ concentration gradient was reversed, but was little affected if the Na+ gradient was decreased by 25 or 50%. Recovery from a Ca2+ load caused by reversal of the Na+ gradient could be induced by removal of Cao2+ in the continuing absence of Nao+, indicating the importance of a Na(+)‐independent [Ca2+]i‐lowering system. 6. The results demonstrate that Na(+)‐Ca2+ exchange can modulate [Ca2+]i when [Na+]i and the membrane potential are set at or near their physiological levels in these smooth muscle cells. [Ca2+]i does not, however, appear to be markedly sensitive to the Na+ concentration gradient under the conditions employed for these experiments, suggesting that a Na(+)‐independent Ca2+ extrusion system is mainly responsible for regulating [Ca2+]i under normal conditions.
Corticofugal action on transmission of group I input from the hindlimb to the pericruciate cortex in the cat.
Authors: McIntyre A K , Proske U , Rawson J A
Published: December 2014

1. In cats anaesthetized with alpha‐chloralose, evidence was sought for a corticofugal action on input from muscle group I afferents projecting to the cerebral cortex via the brain stem relay at nucleus Z. 2. Extracellular recordings were made of responses of thirty‐four nucleus Z neurones which could be activated by stimuli at group I strength applied to each of a variety of hindlimb muscle nerves. Afferent input to each nucleus Z neurone was restricted to a single muscle. 3. Nucleus Z neurones typically showed a resting discharge which could be increased or decreased by altering the amount of stretch on the muscle which was the source of the afferent input. Ventral root stimulation gave response patterns which showed these neurones to be driven by input from either tendon organs or muscle spindles, but not both. 4. A brief train of focal, cathodal stimuli applied to a discrete region of pericruciate cortex could consistently inhibit the maintained activity evoked by muscle stretch in nucleus Z neurones, or the response evoked by stimulation of the muscle nerve at group I strength. The inhibition was powerful and lasted 50‐400 ms. The effective stimulating site corresponded to area 3a, the main cortical receiving area for hindlimb muscle group I input. 5. Since the ascending spinal axons which project to nucleus Z are collaterals of dorsal spinocerebellar tract fibres, it was possible to stimulate the parent axons at their termination in the anterior lobe of the cerebellum. Cortical stimulation was found to have little or no effect on activity in nucleus Z neurones evoked by cerebellar stimulation over conditioning‐test intervals in the range 10‐200 ms. 6. It is concluded that over the time intervals for which it has been tested, corticofugal inhibitory action appears to be largely operating at the first spinal segmental relay, in Clarke's column. Thus the inhibitory action arising in area 3a of the cerebral cortex will suppress the action of input from hindlimb group I fibres at the level both of the cerebellum and the cerebral cortex.
Baroreceptor‐vasomotor reflex after N‐methyl‐D‐aspartate receptor blockade in rabbit caudal ventrolateral medulla.
Authors: Blessing W W
Published: December 2014

1. Experiments were performed in anaesthetized rabbits to determine whether blockade of N‐methyl‐D‐aspartate receptors in the caudal ventrolateral medulla oblongata prevents the changes in renal sympathetic vasomotor activity which normally occur in response to increases or decreases in arterial pressure. 2. N‐Methyl‐D‐aspartic acid receptor blockade using bilateral injections of either kynurenic acid (5 nmol) or DL‐amino‐5‐phosphonovaleric acid (5 nmol) caused a rise in arterial pressure with a variable change in renal sympathetic nerve activity. 3. The depressor and renal sympathoinhibitory responses normally seen after intramedullary injection of N‐methyl‐D‐aspartic acid (50 pmol) into the caudal ventrolateral medulla were entirely prevented by prior receptor blockade. The corresponding responses to L‐glutamate (10 nmol) were not affected. 4. The depressor and renal sympathoinhibitory responses normally seen with electrical stimulation of the aortic depressor nerve were abolished by the receptor blockade. 5. The reflex inhibition of renal sympathetic nerve activity normally seen in response to increasing arterial pressure using a cuff around the descending aorta was not affected by kynurenic acid. The response was reduced by DL‐amino‐5‐phosphonovaleric acid but a significant degree of inhibition was preserved. The reflex increase in renal sympathetic nerve activity normally seen in response to reducing arterial pressure using a cuff occluder around the inferior vena cava was unchanged after injection of DL‐amino‐5‐phosphonovaleric acid and was increased in magnitude after injection of kynurenic acid. 6. The results indicate that blockade of excitatory amino acid receptors in the caudal ventrolateral medulla of the rabbit abolishes the depressor response evoked by electrical stimulation of the aortic nerve but leaves intact the normal baroreceptor‐vasomotor responses elicited by raising or lowering arterial pressure.
Intrinsic properties of nucleus reticularis thalami neurones of the rat studied in vitro.
Authors: Avanzini G , de Curtis M , Panzica F , Spreafico R
Published: December 2014

1. Neurones of the nucleus reticularis thalami of the rat were studied by intracellular recordings from in vitro slices. The resting membrane potential was ‐56.28 +/‐ 5.86 mV (mean value +/‐ S.D.); input resistance was 43.09 +/‐ 9.74 M omega; the time constant tau was 16.51 +/‐ 3.99 ms. At the resting membrane potential tonic firing is present, while at membrane potentials more negative than ‐60 mV a burst firing mode gradually prevails. 2. Prolonged depolarizing current pulses superimposed on a steady hyperpolarization consistently activated sequences of burst‐after‐hyperpolarization complexes. The all‐or‐none burst response consisted of Na+‐mediated, TTX‐sensitive fast action potentials superimposed on a low threshold spike (LTS). The burst was followed by a stereotyped after‐hyperpolarization lasting 100‐120 ms (BAHP), with a maxima ‐85 mV. The BAHP was blocked by Cd2+ and apamine but not by 8‐Br cyclic AMP. The early component of BAHP was significantly attenuated by TEA. The oscillatory rhythmic discharges were abolished by agents which blocked the BAHP. 3. The presence of strong after‐hyperpolarizing potentials (SAHP and BAHP) in RTN neurones plays a significant role in determining two different functional states, defined as tonic and oscillatory burst firing modes, respectively.
Role of the sodium pump in pacemaker generation in dog colonic smooth muscle.
Authors: Barajas-López C , Chow E , Den Hertog A , Huizinga J D
Published: December 2014

1. The role of the Na+ pump in the generation of slow wave activity in circular muscle of the dog colon was investigated using a partitioned ‘Abe‐Tomita’ type chamber for voltage control. 2. Blockade of the Na+ pump by omission of extracellular K+, by ouabain, or the combination of 0 mM‐Na+ and ouabain, depolarized the membrane up to approximately ‐40 mV and abolished the slow wave activity. Repolarization back to the control membrane potential by hyperpolarizing current restored the slow wave activity. 3. Slow waves continued to be present in 0 Na+, Li+ HEPES solution. 4. The depolarization induced by the procedures to block Na+ pump activity was associated with an increase in input membrane resistance. 5. Voltage‐current relationships show the presence of an inward rectification. 6. Reduction of temperature depolarized the membrane, and decreased the slow wave frequency and amplitude. The slow wave amplitude was restored by repolarization of the membrane. 7. Brief depolarizing pulses evoked premature slow waves. Brief hyperpolarizing pulses terminated the slow waves. 8. We conclude that abolition of slow wave activity by Na+ pump blockade is a direct effect of membrane depolarization and that the Na+ pump is not responsible for the generation of the slow wave. 9. Our results are consistent with the hypothesis that pacemaker activity in smooth muscle is a consequence of membrane conductance changes which are metabolically dependent.