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Biomedical subjects

D A Terrar

Publications and source records attributed to D A Terrar.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effects of halothane on membrane currents associated with contraction in single myocytes isolated from guinea-pig ventricle.

1. The effects of halothane on electrical activity and contraction were investigated in single myocytes isolated from guinea-pig ventricle. 2. Halothane depressed the plateau and shortened the duration of action potentials. 3. Halothane also reduced the amplitude of inward calcium currents and of additional inward current activated by cytosolic calcium under voltage-clamp conditions. 4. Contractions (measured by an optical technique) accompanying either action potentials or calcium currents were reduced by halothane. However, the extent of attenuation of contraction was greater than when a similar level of calcium channel blockade was induced by application of verapamil. 5. Actions of halothane on calcium-activated tail currents in double-pulse experiments were consistent with reduction by halothane of the cytosolic calcium transient, perhaps as a consequence of reduced uptake of calcium into sarcoplasmic reticulum stores. 6. It is concluded that the actions of halothane on inward currents contribute to its effects on action potentials. The reduction in contraction caused by halothane may result partly from a reduced influx of calcium to trigger contraction, and partly by a reduced release of calcium from sarcoplasmic reticulum stores.

Animals↗
PubMed1988

Influence of halothane on electrical coupling in cell pairs isolated from guinea-pig ventricle.

1. The actions of halothane on electrical coupling between cells were investigated in cell pairs isolated from guinea-pig ventricular muscle. 2. Under voltage-clamp conditions a step depolarization applied to one cell caused a similar change in potential in the second. Application of halothane led to the appearance of double peaks in inward current evoked by step depolarizations. These observations were interpreted in terms of uncoupling of the cells leading to escape of the second cell from the influence of the voltage-clamp in the first cell. 3. This suggestion that uncoupling in the presence of halothane led to differences in electrical activity in the two cells was confirmed in experiments in which independent electrodes were used to measure membrane potential in the two cells. 4. The voltage responses of both cells of the pair were recorded in response to constant current pulses. Administration of halothane led to abolition of the response recorded from the second cell while that of the first was enhanced. The actions are consistent with an action of halothane on gap junctions to block electrical coupling. 5. Qualitatively similar observations, consistent with electrical uncoupling, were observed with isoflurane. 6. These findings may be significant in relation to the arrhythmogenic actions of halothane.

Animals↗
PubMed1987

Electrical activity and contraction in cells isolated from rat and guinea-pig ventricular muscle: a comparative study.

1. Contraction in single ventricular muscle cells from rat and guinea-pig heart was measured using an optical technique, while at the same time either action potentials were recorded or transmembrane currents were measured under voltage-clamp conditions. 2. When the membrane was depolarized to 0 mV, there was a phasic and a tonic component of the contraction in guinea-pig cells, whereas in rat cells only the phasic component was obvious. In both species the depolarizations evoked the second inward current (Isi). 3. In rat cells, when the membrane potential during a depolarization was varied over the range -40 to +60 mV, the amplitude of contraction first increased to a peak at a potential close to 0 mV, and then declined as the membrane potential became more positive. In contrast, contraction in guinea-pig cells measured under similar conditions continued to increase as the depolarization was increased, and the tonic component of contraction became more obvious at more positive potentials. Contraction amplitude in guinea-pig cells could also be increased by increasing pulse duration under conditions where the tonic component of contraction was prominent. 4. Contraction during depolarization was suppressed by ryanodine in rat cells, whereas in guinea-pig cells contraction persisted, but with a modified time course. Ryanodine did inhibit spontaneous contractions of guinea-pig cells during exposure to low extracellular sodium. 5. Nifedipine suppressed Isi and phasic contraction in both rat and guinea-pig cells. In guinea-pig cells these effects developed contemporaneously, but in rat cells substantial reduction of Isi occurred before marked suppression of contraction. 6. In rat cells exposed to strontium in place of external calcium, inactivation of Isi was slowed and contraction was prolonged, with a slower time-to-peak and relaxation. The time course of the action potential was modified and ryanodine no longer inhibited contraction of rat cells in the presence of strontium. 7. It is concluded that the amplitude of contraction in rat and guinea-pig ventricular cells is determined by calcium both entering through the surface membrane and released from internal stores, and that under normal conditions the balance is towards release from stores in rat cells, and towards entry through the surface in guinea-pig cells.

Action Potentials↗
PubMed1987

Calcium-activated inward current and contraction in rat and guinea-pig ventricular myocytes.

1. Single ventricular cells from rat and guinea-pig hearts were voltage clamped, and contraction was monitored with an optical method. 2. In rat cells, short (2-10 ms) depolarizing pulses to 0 mV from a holding potential of -40 mV evoked current carried by calcium, and on repolarization to -40 mV there was a slow 'tail' current which decayed much more slowly than the expected deactivation of calcium current at this potential. 3. When rat cells were loaded with EGTA diffusing into the cytosol from an intracellular electrode, contraction and the tail current were both abolished, whereas the peak calcium current was not reduced. 4. Exposure of rat cells to ryanodine (1-2 microM) suppressed both contraction and the tail current, but not peak calcium current. 5. The tail current was unaffected by tetrodotoxin (10 microM), but was reduced by lowering extracellular sodium to 10% by replacement with lithium or choline. 6. In rat cells, exposure to nifedipine (1-5 microM) initially caused a marked reduction of calcium current while substantial contraction and tail current remained; longer exposure to nifedipine suppressed both contraction and the tail current. Isoprenaline (50-100 nM) caused a marked increase in peak calcium current, while under these conditions there was little or no increase in either contraction or tail current. 7. The amplitude of the tail current in rat cells varied with the duration of the depolarization at 0 mV; the tail current evoked by repolarization to -40 mV reached a peak just as contraction was beginning to develop and was back to undetectable levels just as relaxation became significant, as might be expected if the tail current were determined by the cytosolic calcium transient which triggered contraction. 8. In guinea-pig cells, a tail current was also recorded on repolarization to a holding potential of -40 mV, and, as in rat cells, the tail was suppressed by cytosolic EGTA and reduced by exposure of the cells to low-sodium solution. 9. It is concluded that the tail currents recorded in both rat and guinea-pig cells represent current activated by a rise in cytosolic calcium; in rat cells this is markedly dependent on ryanodine-sensitive release of calcium from internal stores. The origin of this current, and its possible role during the plateaux of action potentials are discussed.

Action Potentials↗
PubMed1986

Electrical properties and response to noradrenaline of individual heart cells isolated from human ventricular tissue.

The analysis of the electrical properties and response to catecholamines of cardiac tissue is greatly simplified by the use of single cell preparations. In this study individual cells isolated from human ventricular tissue were used to estimate cellular sarcolemmal resistance and capacitance and to record the time course of the response to ionophoretically applied noradrenaline. The mean input capacitance of the cells is consistent with a surface membrane area of approximately 15,000 micron2 if the specific membrane capacitance is 1 microF X cm-2. This is larger than might be expected from the measured external dimensions of the cell and is compatible with the presence of surface membrane infoldings and caveolae. At membrane potentials close to -75 mV the mean cell input resistance was approximately 40 M omega, giving a specific membrane resistance of 6 omega X cm2 if mean membrane area is 15,000 micron2 and consistent with the assumption that the isolated cells have sealed intercalated discs under the experimental conditions used. Ionophoretically applied noradrenaline produced a pronounced prolongation of the plateau phase of the action potential, but this effect developed over many seconds. The slow onset of action is not compatible with the kinetics of free extracellular diffusion of catecholamine but may reflect molecular events that occur between noradrenaline binding to membrane receptors and the final cellular response. Under voltage-clamp conditions, the cells showed a time dependent inward current consistent with the rapid activation and decay of a sarcolemmal calcium conductance.

Action Potentials↗
PubMed1985

Influence of a change in stimulation rate on action potentials, currents and contractions in rat ventricular cells.

The effects of a change in stimulation rate on electrical activity and accompanying contraction were investigated in ventricular cells isolated from rat heart; the cells were stimulated to contract either by brief depolarization pulses which evoked action potentials, or, under voltage-clamp conditions, by step depolarizations. An increase in stimulation rate from 0.3 to 3 Hz resulted in a gradual reduction in the amplitude of contraction and attenuation of the late phase of the action potential. These changes were less marked at more depolarized potentials. The ventricular cells were voltage clamped at -40 mV and initially stimulated at 0.3 Hz by step depolarizations to 0 mV for 10 or 100 ms, which activated the second inward current (Isi) and an accompanying contraction. The amplitude and time course of contraction were similar with the two pulse durations. When the duration of the depolarization was 100 ms, an increase in stimulation rate to 3 Hz caused a gradual decline in the amplitude of Isi and of the evoked contraction; at the same time extra contractions and small, transient inward currents appeared in addition to the evoked contractions and Isis. There was a reduction in the early component of decay of Isi at 3 Hz. With a depolarizing pulse duration of 10 ms, an increase in stimulation rate to 3 or to 4.2 Hz did not change the amplitude of the evoked Isi or contraction and no extra contractions or currents appeared. Intracellular EGTA abolished all contractions in the cells and an increase in the rate of stimulation with 100 ms pulses did not then induce transient inward currents. There was some decrease in the Isi amplitude but this was not as marked as in the absence of EGTA and the time course of current decay was similar at the two rates. Ryanodine prevented the appearance of extra contractions and currents when the stimulation rate was increased to 3 Hz and, as in the presence of intracellular EGTA, there was a small decrease in Isi amplitude while the time course of decay was similar at the two stimulation rates. The time course of recovery of Isi from inactivation, as shown by a double-pulse procedure, was altered when the duration of the first pulse was reduced from 100 to 10 ms, an extra inactivation of Isi being seen at pulse intervals of 20-100 ms. This extra component of inactivation was not seen with intracellular EGTA or in the presence of ryanodine.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1984

The effects of ryanodine, EGTA and low-sodium on action potentials in rat and guinea-pig ventricular myocytes: evidence for two inward currents during the plateau.

Action potentials were recorded from single cells isolated from rat and guinea-pig ventricular muscle. In rat cells the repolarization showed two distinct phases, referred to as the early and late phases. In guinea-pig cells there was a maintained plateau. Reducing external sodium by replacement with lithium or choline suppressed the late phase of the action potential in rat cells, and shortened the plateau of the action potential in guinea-pig cells. Intracellular EGTA abolished contraction while suppressing the late phase of the action potential in rat cells, and shortening the plateau in guinea-pig cells. Ryanodine (1 microM), which is thought to inhibit the release of calcium from internal stores, suppressed contraction and the late phase of the action potential in rat cells. In guinea-pig cells, there was no substantial effect of ryanodine (1 microM) on either contraction or the time course of the action potential. The late phase of the action potential in rat cells was suppressed by increasing the external potassium concentration to 12 mM, and enhanced by reducing external potassium to 1.2 mM. It is concluded that an inward current activated by internal calcium contributes to the late phase of the action potential in rat cells, and to the plateau in guinea-pig cells. Two possibilities are a current arising from electrogenic sodium-calcium exchange, and a current through ion channels activated by calcium. The effects of reducing external sodium would be consistent with either mechanism. The contribution of such an inward current would be expected to be modified by outward currents through a rectifying potassium conductance which varies with external potassium concentration. In the rat, but not the guinea-pig, the rise in internal calcium which activates the inward current seems to be largely dependent on ryanodine-sensitive release of calcium from internal stores.

Action Potentials↗
PubMed1984

Strontium, nifedipine and 4-aminopyridine modify the time course of the action potential in cells from rat ventricular muscle.

Action potentials, initiated by brief depolarizing pulses, were recorded from single cells isolated from rat ventricular muscle. These action potentials showed a rapid upstroke to about +30 mV, followed by two phases of repolarization referred to as the early and late phases of the action potential. Nifedipine (1 microM), which blocks the second inward current (Isi) carried by Ca in these cells, shortened the early phase. Substitution of strontium for calcium in the solution bathing the cells, a procedure which prolongs Isi, prolonged the early phase. 4-Aminopyridine (1 mM), which inhibits transient outward current, prolonged the early phase with either calcium or strontium in the external solution. It is concluded that both Isi and transient outward current contribute to the early phase of the action potential in rat ventricular muscle. It is also suggested that Isi does not directly contribute to the late phase, since the characteristics of the late phase are not compatible with such a role, and the possibility of additional inward current is investigated in the accompanying paper (Mitchell et al., 1984).

4-Aminopyridine↗
PubMed1984

Ryanodine prolongs Ca-currents while suppressing contraction in rat ventricular muscle cells.

Ryanodine (1 microM) suppressed or abolished contraction in response to step depolarization in voltage-clamped cells isolated from adult rat ventricular myocardium. The step depolarizations evoked the second inward current, which is carried largely by Ca ions under these conditions, and there was little or no change in the amplitude of this current when contraction was reduced or abolished by ryanodine. The effects of ryanodine on contraction were, however, accompanied by a prolongation of the second inward current resulting from a slowing of the apparent inactivation of this current. It is suggested that ryanodine affects steps in excitation-contraction coupling subsequent to the second inward current, perhaps Ca-release from intracellular stores, and that this slows a Ca-dependent inactivation of second inward current.

Alkaloids↗
PubMed1984

Nature of the anticholinesterase-induced repetitive response of rat and mouse striated muscle to single nerve stimuli.

The action of the anticholinesterase Paraoxon on neuromuscular transmission in rat diaphragm and mouse omohyoideus preparations was investigated. In both preparations, when Paraoxon potentiated the twitch in response to a single nerve stimulus, repetitive muscle action potentials were recorded with an intracellular electrode placed at the motor end-plate region. At end-plates of Paraoxon-treated rat diaphragm preparations where the membrane potential was not sufficiently negative to support muscle action potentials, repetitive end-plate potentials were recorded in response to a single nerve stimulus. No repetitive end-plate potentials could be recorded under such conditions in preparations which had been exposed to dithiothreitol before being treated with Paraoxon, although twitch potentiation and repetitive muscle action potentials were still observed in these preparations. In Paraoxon-treated mouse omohyoideus preparations only single end-plate potentials were recorded from end-plates where the membrane potential was not sufficiently negative to support muscle action potentials. This applied whether or not the preparation had been treated with dithiothreitol before being exposed to Paraoxon. In voltage-clamped rat diaphragm preparations which had been treated with Paraoxon, repetitive end-plate currents were frequently recorded in response to a single nerve stimulus. Under the same conditions mouse omohyoideus preparations responded with a single end-plate current. It is concluded that Paraoxon-induced twitch potentiation in rat diaphragm and mouse omohyoideus preparations is caused by repetitive muscle action potentials being triggered by a single nerve stimulus. Under the conditions stated, the repetitive muscle action potentials in rat diaphragm preparations arose from a prolonged end-plate potential or repetitive end-plate potentials or a combination of both. In mouse omohyoideus preparations the repetitive muscle potentials were the consequence of a single prolonged end-plate potential.

Action Potentials↗
PubMed1983

Characteristics of the second inward current in cells isolated from rat ventricular muscle.

The second inward current (Isi) in single cells isolated from ventricular muscle of adult rat hearts was measured in response to step depolarizations under voltage-clamp conditions. The major ion carrying this current was Ca, and Isi was reduced or abolished by Mn, Ni, Cd, nifedipine, nimodipine and D600. Sr and B could substitute for Ca as charge carriers, and reduced the rate of apparent inactivation of Isi. These effects of Sr and Ba, together with the relation between the steady level of apparent inactivation and membrane potential in Ca containing solution, were taken as evidence that inactivation was at least in part dependent on internal Ca. The reduction of external Na to 11% of normal caused a reduction in peak Isi when Ca was present in the external solution, but did not reduce Isi when Ca was replaced by Sr. It therefore seems unlikely that Na is a major charge carrier for Isi under the conditions of our experiments. The time-to-peak and rate of apparent inactivation of Isi were faster than in previous studies that used multicellular preparations. Both the kinetics and peak amplitude of Isi were markedly dependent on temperature (Q10 close to 3). Contraction of the cells, which was monitored optically, was initiated within 3 ms of the peak Isi, reached a maximum level after approximately 40-50 ms, and was about 100 ms in duration.

Animals↗
PubMed1983

Effects of pancuronium and hexamethonium on paraoxon-induced twitch potentiation and antidromic firing in rat phrenic nerve diaphragm preparations.

The actions of pancuronium, a selective antagonist of acetylcholine (ACh) at nicotinic cholinoceptors at motor endplates, and hexamethonium, a selective antagonist of ACh at nicotinic cholinoceptors in autonomic ganglia, have been studied in rat phrenic nerve diaphragm preparations. The effects on paraoxon-induced twitch potentiation and antidromic firing (ADF) in the phrenic nerve, were compared with the effects on normal twitch tension and intracellularly recorded miniature endplate potentials (m.e.p.ps) and endplate potentials (e.p.ps.) In preparations exposed to paraoxon, pancuronium was found to be approximately 10 times more effective in reducing the potentiated component of the twitch than the component which corresponded to the pre-paraoxon twitch. A similar result was obtained with hexamethonium. Pancuronium and hexamethonium, in concentrations which reduced paraoxon-induced twitch potentiation but had no effect on the twitch tension of preparations not treated with paraoxon, reduced paraoxon-induced ADF. The lowest concentrations of pancuronium and hexamethonium required for this also reduced the amplitude of m.e.p.ps and e.p.ps. Dithiothreitol, a disulphide bond reducing agent which reduces the affinity of ACh for nicotinic cholinoceptors, enhanced the potency of pancuronium 2 to 3 fold. The same also applied for hexamethonium. It is concluded that the experiments failed to provide evidence for an action of ACh on prejunctional nicotinic cholinoceptors of the ganglionic-type being involved in the initiation by paraoxon of twitch potentiation and ADF. Furthermore, the results obtained can be explained by pancuronium and hexamethonium reducing the action of ACh at the postjunctional membrane.

Animals↗
PubMed1983

The relationship between stimulus-induced antidromic firing and twitch potentiation produced by paraoxon in rat phrenic nerve-diaphragm preparations.

The relationship between stimulus-induced repetitive antidromic firing (ADF) in the motor nerve and twitch potentiation produced by the organophosphate anticholinesterase paraoxon, has been investigated in rat diaphragm preparations. Little or no ADF was produced by paraoxon in preparations bathed in a Tyrode solution containing 1 mM calcium and 1 mM magnesium ions although the preparations showed marked twitch potentiation. Increases in the calcium:magnesium ion ratio produced a ratio-dependent increase in the ADF but had no consistent effect on peak twitch potentiation. Dithiothreitol, a disulphide bond reducing agent which decreases the affinity of acetylcholine for nicotinic cholinoceptors, abolished ADF but only modified the time course of twitch potentiation. Dithiothreitol, a disulphide bond reducing agent which decreases the affinity of acetylcholine for nicotinic cholinoceptors, abolished ADF but only modified the time course of twitch potentiation. It is concluded that the initiation of ADF is a consequence of the prolonged action of acetylcholine within the synaptic cleft following inhibition of acetylcholinesterase, and that ADF is not the only mechanism by which twitch potentiation can be produced.

Animals↗
PubMed1981

Intact individual heart cells isolated from human ventricular tissue.

The intricate architecture of heart muscle, comprising irregularly shaped cells which interdigitate in a complex three-dimensional array, has often compromised clear interpretation of experimental data obtained from the whole organ. One approach to minimise some of the difficulties is to use individual muscle cells in suspension, and data have already been reported using myocytes isolated from mammalian ventricles. It is difficult, however, to extrapolate results obtained from animal tissues to situations of medical relevance in man. Intact isolated muscle cells were obtained from human ventricular tissue by modifications of methods used for isolating smooth muscle, atrial, and ventricular tissue from animals. Electrical studies showed that these myocytes had functional characteristics similar to those observed in the whole heart. Such cells will prove a useful preparation for studies on both the mechanisms underlying myocardial performance in normal and diseased states and the response of heart tissue at the cellular level to conditions found during cardiac surgery.

Action Potentials↗
PubMed1981

The effect of (+)-tubocurarine on neuromuscular transmission during repetitive stimulation in the rat, mouse, and frog.

1. The effect of tubocurarine on amplitudes of end-plate currents in response to trains of repetitive stimulation (50-150/sec) was investigated in voltage-clamped muscle fibres of the rat, mouse and frog. 2. In rat and mouse muscle, the presence of tubocurarine led to a more rapid decline (rundown) in the amplitudes of successive end-plate currents during trains of impulses. In frog, tubocurarine caused an increase in apparent facilitation of end-plate current amplitudes during the first few impulses of repetitive stimulation; this increase was followed by a more rapid rundown of end-plate current amplitude. 3. These effects of tubocurarine appear not to be an artifact resulting from inadequate control of membrane potential in voltage-clamped fibres. 4. The more rapid rundown during trains of end-plate currents in the presence of tubocurarine showed little variation with membrane potential indicating that voltage-sensitive channel blockade by tubocurarine was not a major factor contributing to the rundown. 5. The effect of tubocurarine on the apparent facilitation and rundown of end-plate current amplitudes was typically decreased by reducing the frequency of stimulation. 6. These results suggest that tubocurarine affects transmitter release at neuromuscular junctions during repetitive stimulation.

Animals↗
PubMed1980

Electrical properties of individual cells isolated from adult rat ventricular myocardium.

1. Individual cells were isolated from adult rats ventricular myocardium by a collagenase digestion procedure. 2. Steady membrane potentials recorded with conventional intracellular glass micro-electrodes from cells in a modified Krebs solution containing 3 . 8 mM-KCl and 0 . 5 mM-CaCl2 were less negative than -40 mV in most cells (-25 . 3 +/- 10 . 9 mV, mean +/- S.D., 211 cells). 3. After addition of the potassium selective ionophore valinomycin (60 nM) to the bathing solution all recorded membrane potentials were more negative than -60 mV (-74 . 8 +/- 7 . 0 mV, sixty-three cells). 4. The internal concentration of potassium in the cells was determined as 120 . 8 +/- 1 . 7 mM (+/- S.E., n = 24) by flame emission spectrometry after centrifugation through silicone oil, using tritiated water and D-[1-14C] mannitol to estimate total and extracellular water in the pellet. 5. In the majority of cells in the standard solution the membrane potential recorded within a few msec of penetration was more negative than -70 mV (-78 . 4 +/- 9 . 7 mV, seventy-three cells). In sixty-six cells penetration initiated an action potential which overshot zero by 31 . 3 +/- 7 . 1 mV. This overshoot was abolished by reducing the external sodium to 0 . 1 of the normal value, and reduced or abolished by addition of tetrodotoxin (30 microM). 6. Modifications of the standard bathing solution which increased the number of cells with steady recorded membrane potentials more negative than -60 mV were: isosmotic substitution of sucrose for NaCl; replacement of NaCl and KCl by sodium isethionate and potassium methyl sulphate; addition of 5 or 10 mM-CaCl2; addition of 10 mM-MnCl2. 7. For cells in solution containing 2 . 5 or 5 . 5 mM-CaCl2, input resistances estimated from the amplitude of hyperpolarizations evoked by 200 msec current pulses were approximately 40 M omega at a resting potential close to -80 mV and became much greater as cells were depolarized. Time constants measured at the resting potential were approximately 8 msec. 8. In certain conditions, repeated spontaneous action potentials were recorded from contracting cells, and in quiescent cells evoked action potentials could be initiated by applying brief depolarizing pulses through the micro-electrode. Action potentials were coincident with contractions. 9. It is concluded that the resting potential of these isolated cells is normally more negative than -70 mV, and that the cells retain the ionic mechanisms necessary for the generation of active currents.

Animals↗
PubMed1978

Effects of dithiothreitol on end-plate currents.

1. End-plate currents have been studied in frog cutaneus pectoris nerve-muscle preparations mounted in continuously flowing solution, using the voltage clamp technique. 2. Exposure of the muscle to 1 mM-dithiothreitol reduced the amplitude of end-plate currents by a factor of 2.7 (mean; range 1.6-3.4; twelve fibres). 3. 1 mM-dithiothreitol also caused a 2.7-fold (2.3-3.1) increase in the rate of decay, and a 1.4-fold (1.3-1.6) decrease in the time to peak of end-plate currents. During the onset of action of dithiothreitol, there was little or no indication of departure of end-plate current decay from a simple exponential. 4. Dithiothreitol actions on amplitude and decay of end-plate currents developed with similar time courses and both effects were slower in onset at pH 7.2 than at pH 8.5. 5. The actions of dithiothreitol were reversed by exposure of the muscle to 1 mM-5,5'-dithio-bis-(2-nitrobenzoic acid). 6. Following dithiothreitol treatment, the rates of decay of end-plate currents continued to depend on membrane potential; there was little or no change in the slope of the relation between in (rate of decay) and membrane potential, consistent with little or no change in the dipole moment of a gating molecule for ion channels. 7. Dithiothreitol changed the relation between peak end-plate current and membrane potential, so that peak conductance increased at more negative membrane potentials; this finding could be accounted for in terms of the closure of ion-channel gates becoming faster though remaining voltage-sensitive after exposure to dithiothreitol. 8. It is concluded that dithiothreitol causes changes in the kinetics of gating of ion channels associated with receptors and that these changes accompany changes in the binding of ACh to receptors.

Animals↗