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D A Terrar

Publications and source records attributed to D A Terrar.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effect of glibenclamide, forskolin, and isoprenaline on the parallel activation of KATP and reduction of IK by cromakalim in cardiac myocytes.

OBJECTIVE: The aim was to investigate the effect of activation of ATP sensitive potassium channels by cromakalim on the delayed rectifier potassium current (IK) in guinea pig ventricular myocytes. Experiments were carried out in the absence and presence of forskolin or isoprenaline to promote phosphorylation of IK, and in the presence of glibenclamide to block the ATP sensitive potassium current (IK(ATP)). METHODS: Single cells were isolated from guinea pig ventricle. Potassium currents were studied under voltage clamp conditions. The delayed rectifier was measured as an outward tail current upon repolarisation to a holding potential of -40 mV following depolarising steps to +40 mV. Induction of IK(ATP) was indicated by changes in the holding current. RESULTS: Exposure to 20 microM cromakalim caused a significant increase of 244(SEM 47)% in the holding current and simultaneous decreases of 22(5)% in the rapid component (IKr) and 45(5)% in the slow component (IKs) of IK. Exposure of the cells to 5 microM forskolin or 100 nM isoprenaline reduced both these effects of cromakalim: with forskolin, the holding current increased by 59(17)%, IKr was reduced by 9(3)%, and IKs by 23(3)%; with isoprenaline, the holding current increased by 100(36)%, IKr was not significantly changed, and IKs was reduced by 27(5)%. With 10 microM glibenclamide present, the only significant effect of cromakalim was reduction of IKs [by 11(3)%]. CONCLUSIONS: Cromakalim caused decreases in both components of IK which developed in parallel with activation of IK(ATP). The observations that forskolin, isoprenaline, or glibenclamide all reduced the effects of cromakalim on both IK and IK(ATP) may result from separate effects on the two channel pathways, but are also consistent with the single hypothesis that cromakalim induces an interconversion of potassium channels which is reduced when potassium channels are modified by these three drugs.

Animals↗
PubMed1994

The effects of propofol and enflurane on single calcium channel currents of guinea-pig isolated ventricular myocytes.

1. The effects of the anaesthetics, propofol (100 microM) and enflurane (3%, 1.46 mM), on single L type calcium channel currents were investigated in single myocytes isolated from guinea-pig ventricles. Channel activity was recorded from membrane patches by use of the 'cell-attached' patch-clamp technique (pipette solution containing 110 mM BaCl2, 5 microM Bay K 8644, 5 microM HEPES, pH 7.4; temperature 36 degrees C). 2. Channel conductance was calculated from the slope of the relationship between single channel current and membrane potential during step depolarizations to activate the channel over a range of approximately -20 to +20 mV. Neither propofol (6 cells) nor enflurane (7 cells) caused any significant reduction in channel conductance. 3. Both propofol (7 cells) and enflurane (9 cells) decreased the probability of the channel being open during depolarizations to +10 mV (measured from histograms of the fraction of time spent by the channel at different current levels, taking areas under the Gaussian curves fitted to the open and closed components of the distributions to represent the proportion of time spent in the two states). 4. A fraction of the current traces showed no detectable channel openings in response to step depolarizations to +10 mV. Both propofol and enflurane significantly increased the fraction of silent traces. 5. Transitions across a threshold halfway between the open and closed levels were used to define periods spent in the open and closed states. Both propofol (7 cells) and enflurane (9 cells) reduced the mean open times and increased the mean closed times of the calcium channel. 6. Histograms were plotted showing the distributions of times spent by the channels in the open and closed states. Two exponentials were fitted to the open and closed time distributions. Both propofol (7 cells) and enflurane (9 cells) shortened both time constants fitted to the open times and lengthened both time constants fitted to the closed times.7. It is concluded that both propofol and enflurane appear to alter the kinetics of opening and closing of calcium channels to favour shut channels without altering channel conductance. This effect would be expected to result in a reduction of the macroscopic calcium current and thus contribute to the negative inotropic action of these anaesthetics.

Animals↗
PubMed1993

The positive inotropic effect of compound II, a novel analogue of sotalol, on guinea-pig papillary muscles and single ventricular myocytes.

1. Compound II is a novel analogue of sotalol which has been reported to be free of beta-adrenoceptor and L-type calcium channel blocking actions. The effects of compound II on the contraction of guinea-pig papillary muscles (at 2 microM) and single ventricular myocytes (at 100 nM) were investigated. 2. Exposure to compound II caused a significant increase in the contraction of both preparations. 3. Compound II prolonged the action potential of the single myocytes and increased the magnitude of the Ca-activated current which was used as a qualitative indicator of the intracellular calcium transient. 4. The ratio of first/steady state Ca-activated currents evoked by short action potentials was not modified. This may indicate that compound II does not influence the normal functioning of the sarcoplasmic reticulum stores. 5. The observations are consistent with the hypothesis that action potential prolongation by compound II reduces Ca2+ extrusion via the Na-Ca exchange. This in turn allows increased uptake of calcium into the sarcoplasmic reticulum stores so that more calcium is available for release by subsequent action potentials, leading to an increase in intracellular calcium transients and contractions.

Action Potentials↗
PubMed1993

Differential effects of propofol and enflurane on contractions dependent on calcium derived from the sarcoplasmic reticulum of guinea pig isolated papillary muscles.

We investigated the possibility that the effects of propofol on sarcoplasmic reticulum (SR) function may contribute to the myocardial depression induced by this anesthetic. With guinea pig isolated papillary muscles, the effects of propofol on transient alterations in contractility (termed "potentiated-state" contractions), after abrupt changes in stimulation frequency and brief periods of rest, were compared with those of enflurane and the inhibitor of SR function, ryanodine. These potentiated-state contractions are mediated by calcium derived largely from the SR. Propofol, enflurane, and ryanodine were applied at concentrations that produced approximately 50%-60% inhibition of "steady-state" contraction. Ryanodine abolished and enflurane attenuated the potentiated-state contractions, whereas propofol had no apparent effect. Although impairment of SR function may contribute to the depression of contractility induced by enflurane, propofol has no major effect on SR function.

Animals↗
PubMed1992

Effects of propofol and enflurane on action potentials, membrane currents and contraction of guinea-pig isolated ventricular myocytes.

1. The effects of two general anaesthetics, propofol and enflurane, on electrical activity and contractions were investigated in single myocytes isolated from guinea-pig ventricles. 2. Propofol and enflurane depressed the plateau and shortened the duration of action potentials. 3. Under voltage-clamp conditions, propofol and enflurane reduced the amplitude of inward calcium current and of additional inward current activated by cytosolic calcium. 4. Contractions (measured with an optical technique) accompanying either action potentials or second inward currents (in response to depolarizations to 0 mV) were reduced by both anaesthetics. The mechanisms for calcium entry during contractions accompanying pulses to positive potentials such as +60 mV are thought to differ from those accompanying second inward currents which are evoked by pulses from -40 to 0 mV. Enflurane enhanced the amplitudes of contractions accompanying pulses to positive potentials; in contrast these contractions were depressed by propofol. 5. In experiments where recovery processes were investigated by use of pairs of voltage-clamp pulses with a variable interval between them, enflurane but not propofol slowed the recovery of contractions and calcium-activated 'tail' currents. These observations are consistent with the hypothesis that enflurane may impair calcium handling by the sarcoplasmic reticulum whereas propofol has little, if any, effect at this site. 6. In conclusion, the actions of propofol and enflurane on second inward currents contribute to their effects on action potentials and contraction. The negative inotropic effect of both anaesthetics may result partly from reduced calcium influx to trigger contraction, and for enflurane, partly from an impairment of calcium handling by the sarcoplasmic reticulum.

Animals↗
PubMed1992

Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.6. Submaximal concentrations of compound II were without effect on activation of IK with time at a membrane potential of + 40 mV, and no changes were detected in the time constants of the two components of IK decay over the range of potentials - 60 to 0 mV. Compound 11 (50 nM) appeared to cause a small shift in the activation of IK with membrane potential (an apparent shift of approximately 10mV in the depolarizing direction at the mid-point of the curve).7. Log dose-response curves for action potential prolongation and for blockade of IK by compound II were similar. The IC50 for compound II was approximately 30 nM.8. It is concluded that this novel series of compounds prolongs action potential duration, and that in the case of compound II the evidence supports a potent selective effect on the time-dependent potassium current IK, an effect which can account for this prolongation.

Action Potentials↗
PubMed1992

Inactivation of Ca current during the action potential in guinea-pig ventricular myocytes.

The inactivation of Ca channels during the action potential plateau of guinea-pig ventricular myocytes was investigated by interrupting action potentials with voltage clamp pulses to assess Ca channel availability. The influence of the bulk cytosolic calcium [( Ca]i) transient on Ca channel inactivation was also studied by impaling cells with microelectrodes containing the Ca chelator BAPTA (1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; 125-200 mM). Ca channel availability decreased progressively with action potential duration, reaching approximately 20% of maximum availability after 100 ms and falling close to zero at the end of the plateau. When membrane potential became more negative than -40 mV Ca channel availability increased. Elevation of the action potential plateau to more positive levels increased Ca channel availability (even though this was expected to increase peak [Ca]i). When the cytosol was loaded with BAPTA Ca channel availability during the plateau increased. Inactivation of Ca channels was not, however, abolished. The observations are consistent with the hypothesis that in guinea-pig ventricular myocytes the majority of Ca channels are inactivated during the plateau and recovery does not occur until repolarization is almost complete. It may be that while the cytosolic Ca transient (that is generated in part by release of Ca from the intracellular Ca stores) modulates Ca channel availability, significant inactivation of the Ca channel during the action potential plateau is due to voltage dependent inactivation and to Ca-induced inactivation resulting from the Ca which enters the myocyte via Ca channels.

Action Potentials↗
PubMed1991

The synthesis and potassium channel blocking activity of some (4-methanesulfonamidophenoxy)propanolamines as potential class III antiarrhythmic agents.

The synthesis of 22 (4-methanesulfonamidophenoxy)propanolamines and their testing on isolated guinea pig cardiac myocytes, on isolated preparations from guinea pig atria, and on rat blood pressure are described. Secondary amines in the series (11a-f) showed residual beta-blocking activity, whereas incorporation of N-methyl phenylalkyl and 4-phenyl alicyclic amine groups abolished beta-blocking activity but led to enhanced ability to block the channel conducting the delayed rectified potassium current, and hence produced an increase in the cardiac action potential duration (APD). Incorporation of hydrophobic Cl and CF3 groups further enhanced potassium channel blocking activity. Compounds 81 and 8m produced a significant increase in APD at nanomolar concentrations, with no effect on cardiac muscle conduction velocity, and hence merit further investigation as Class III antiarrhythmic agents. Methylation of the methanesulfonamido group abolished channel-blocking activity; 4-carboxy and 3-methanesulfonamido analogues retained activity but at a reduced level.

Animals↗
PubMed1991

Modes of hexamethonium action on acetylcholine receptor channels in frog skeletal muscle.

1. The antagonism between hexamethonium and cholinoceptor agonists was investigated in frog skeletal muscle fibres with voltage-clamp techniques. Hexamethonium caused a voltage-dependent reduction in the amplitude of endplate currents. For neurally evoked endplate currents, the reduction increased e-fold with a 38 mV membrane hyperpolarization. 2. The effect of hexamethonium on the time course of endplate currents was small, and was most apparent as a slight prolongation of the decay phase at hyperpolarized potentials (more negative than -100 mV). A similar small prolongation of single channel lifetime was detected with fluctuation analysis techniques. Hexamethonium produced a voltage-dependent reduction in apparent single channel conductance as the membrane was hyperpolarized. 3. Log (concentration-response) curves for acetylcholine (ACh)-induced currents, determined either from currents accompanying ramp changes in membrane potential or from steady state currents in voltage-jump experiments, were less steep for responses in the presence of hexamethonium. This reduction in slope became more pronounced at more negative membrane potentials. Observations at +50 mV suggested that the equilibrium constant for competitive antagonism was approximately 200 microM. 4. In voltage-jump experiments with a two-microelectrode voltage clamp, the current evoked by ACh in the presence of hexamethonium differed from that recorded with ACh alone. In the presence of hexamethonium, the expected 'instantaneous' ohmic increase in membrane current in response to a hyperpolarizing step was not detected; instead a decrease in current was observed. This problem was further investigated with a vaseline-gap voltage-clamp technique which provides improved temporal resolution. With this method a rapid decrease in the ACh-induced inward current was observed with step hyperpolarizations in the presence of hexamethonium. 5. When the membrane potential was stepped back to its resting level from a more hyperpolarized potential in the presence of hexamethonium, there was a surge of ACh-induced inward current that decayed with a time constant of less than 100 microseconds. 6. The slow relaxation in the ACh-induced current that followed a voltage step recorded in the presence of hexamethonium was slower than that recorded with ACh alone. In the presence of hexamethonium the time constant of this relaxation increased e-fold for a 67 mV hyperpolarization. 7. The results are consistent with a rapid voltage-dependent block of ACh-activated channels by hexamethonium with hyperpolarization, and voltage-dependent unblock with depolarization. The voltagedependent block is combined with competitive antagonism at the ACh receptors. However, not all observations appear to be compatible with a simple sequential block of open ion channels, but rather suggest that occupation of the channel by hexamethonium may not prevent channel closure.

Animals↗
PubMed1991

Action potential duration and the inotropic response to reduced extracellular potassium in guinea-pig ventricular myocytes.

The mechanism of the inotropic effect of a reduction of extracellular potassium from 5.4 to 2.7 mM was investigated in myocytes isolated from guinea-pig ventricle. Action potentials were recorded using intracellular microelectrodes and cell shortening was measured by analysis of a video image. Changes in cytosolic calcium transients were estimated from calcium-activated currents under voltage-clamp conditions. The aim was to determine whether the prolongation of action potential duration which was observed to occur in low potassium might contribute to the increased shortening and increase in calcium-activated current under these conditions. Using a voltage-clamp waveform to mimic the waveform of the action potential, it was found that reduction of potassium caused a marked increase in cell shortening and of calcium-activated current in the absence of prolongation of the 'action potential' waveform. No change in inward calcium current was detected when extracellular potassium was reduced. The sensitivity to strophanthidin appeared to be increased under these conditions. We conclude that prolongation of the action potential is not a major factor contributing to the increased cell shortening and to the increased cytosolic calcium transient when extracellular potassium is reduced.

Action Potentials↗
PubMed1990

The effects of ryanodine and caffeine on Ca-activated current in guinea-pig ventricular myocytes.

1. Action potentials from guinea-pig single ventricular myocytes were interrupted by application of a 300 ms voltage clamp to -40 mV in order to evoke the Ca-activated tail current which is thought to be carried by Na:Ca exchange. Stimulation frequency was 1 Hz and temperature 36 degrees C. 2. The actions of ryanodine (1 microM and 10 microM) and caffeine (1 mM and 10 mM) on Ca-activated tail currents were investigated. 3. Exposure to 10 mM caffeine and ryanodine reduced tail currents associated with very abbreviated (12 ms duration) action potentials and greatly reduced the difference between first and steady-state tail currents at this action potential duration. These observations were interpreted in terms of suppression of Ca release from the sarcoplasmic reticulum (SR) stores. 4. Tail current decay during the voltage clamp is thought to reflect the fall in [Ca]i which accompanies muscle relaxation. Current decay is dependent on Ca extrusion via Na:Ca exchange and on Ca accumulation by the SR stores. Time constants of tail current decay were seen to decrease with increasing action potential duration. This relationship was not affected by 1 mM caffeine or 1 microM ryanodine. Ryanodine at 10 microM and 10 mM caffeine abolished this relationship and increased the time constants of current decay. An increase in the time constant of tail current decay was thought to reflect a reduction in the rate of Ca accumulation by the sarcoplasmic reticulum. 5. The actions of caffeine and ryanodine on the Ca-activated tail currents are consistent with a dose-dependent leakage of Ca from the SR Ca stores. The Ca-activated tail current appears to be a useful tool in the study of Ca homeostasis.

Action Potentials↗
PubMed1990

The action of strophanthidin on calcium-activated current and contraction in single guinea-pig ventricular myocytes.

Calcium-activated tail current was used as a qualitative indicator of changes in [Ca]i in order to investigate the mechanism of strophanthidin-induced inotropy in single guinea-pig ventricular myocytes. Action potentials were interrupted (by application of a voltage clamp to -40 mV) in order to evoke Ca-activated current. Exposure to 10 microM-strophanthidin for 2 min resulted in an increase in contractions associated with complete action potentials and in an increase in Ca-activated current. Strophanthidin appeared not to substantially modify the time course of the envelope of tail currents (recorded by interrupting action potentials at different durations), which is thought to reflect the time course of the systolic [Ca]i transient. Exposure to 1 microM-ryanodine slowed the development of the Ca-activated current envelopes and abolished the above effects of strophanthidin. Exposure to strophanthidin led to reduction in Ca current in a majority of cells (measured by a voltage-clamp step from -40 to 0 mV). These results are consistent with the hypothesis that in single guinea-pig ventricular myocytes strophanthidin causes an increased loading of ryanodine-sensitive intracellular stores of Ca, possibly through reduced extrusion of Ca from the cell by Na-Ca exchange during the action potential plateau.

Action Potentials↗
PubMed1989

Changes in cytosolic calcium monitored by inward currents during action potentials in guinea-pig ventricular cells.

Action potentials were recorded from single cells isolated from guinea-pig ventricular muscle. Contraction was measured with an optical technique. Tail currents thought to be activated by cytosolic calcium were recorded when action potentials were interrupted by application of a voltage-clamp. A family of tail currents was recorded by interrupting the action potential at various times after the upstroke. The envelope of tail current amplitudes was taken as an index of changes in cytosolic calcium. Consistent with this interpretation, tail currents were negligible following intracellular loading with the calcium chelator BAPTA to suppress calcium transients. The cytosolic calcium transient estimated from the envelope of tails reached a peak approximately 50 ms after the upstroke of the action potential, and fell close to diastolic levels before repolarization was complete; 10 mM caffeine delayed the time to peak contraction, and caused a prolongation of the cytosolic calcium transient estimated from the envelope of tail currents. Caffeine also induced the appearance of a distinct late plateau phase of the action potential. Intracellular BAPTA suppressed the late plateau, contraction and tail currents in cells exposed to caffeine. Exposure to caffeine increased the time constant for decay of tail currents (from approximately 25 to 70 ms). When action potentials were greatly abbreviated by interruption with a voltage-clamp, a progressive decline occurred in the subsequent three contractions and tail currents. There was a progressive reversal of these effects over four responses when the full action potential duration was restored. None of these effects was observed in cells exposed to caffeine. Calcium-activated tail currents appear to be a useful qualitative index of changes in cytosolic calcium. The observations are consistent with the suggestion that cytosolic calcium is reduced during the plateau by a combination of calcium extrusion through Na-Ca exchange and calcium uptake into caffeine-sensitive stores. It also appears that reduction of stores loading during abbreviated action potentials reduces subsequent contraction in cells not exposed to caffeine.

Action Potentials↗
PubMed1989

Mechanisms and significance of calcium entry at positive membrane potentials in guinea-pig ventricular muscle cells.

Possible mechanisms for calcium entry at positive membrane potentials were investigated in single cells isolated from guinea-pig ventricular muscle. The cells were voltage clamped and contraction was measured by an optical technique. When prolonged (200 ms to 2 s) depolarizations at +60 mV were applied, contraction amplitude increased with pulse duration, in contrast to the contraction at 0 mV. When a 'pre-pulse' to 0 mV was applied for 200 ms to inactivate current through 'L-type' calcium channels, contraction nevertheless increased with membrane potential during a subsequent test pulse applied over the range -40 to +60 mV. Contraction during the test pulse at +60 mV was abolished when extracellular calcium was reduced to zero. This effect developed more rapidly than abolition of the contraction in response to the pre-pulse to 0 mV. Reduction of extracellular calcium from 2.5 to 1 mM reduced the contraction at +60 mV to a greater extent than that at 0 mV and caused an inward shift in the current at +60 mV. Nifedipine (5 microM) substantially reduced the contraction during the test pulse to 0 mV but had little effect on the contraction at +60 mV. Conversely, dodecylamine (20 microM) caused little or no decrease in the contraction at 0 mV but substantially reduced the contraction at +60 mV. Following a conditioning pre-pulse to 0 mV the contraction at +60 mV was not consistently reduced by exposure to 3 microM-ryanodine. The interpolation of a single 200 ms pulse to +60 mV in a train of pulses to 0 mV potentiated the following contraction to 0 mV. This potentiation decayed over the first four steps to 0 mV following an interpolated pulse and increased with the voltage of the interpolated pulse over the range -20 to +60 mV. Potentiation was abolished on exposure to 3 microM-ryanodine. These observations are consistent with entry of calcium at positive membrane potentials through voltage-dependent, non-inactivating pathways which are insensitive to nifedipine but inhibited by dodecylamine. The observations support the hypothesis that calcium entry via this mechanism may contribute, at least under some conditions, to the loading of intracellular stores of calcium during the late plateau of the action potential, and thus influence subsequent contraction. Calcium entry through Na+-Ca2+ exchange is a possibility which would allow calcium entry to increase over the range of membrane potentials at which contraction was increased. However, additional calcium entry through other nifedipine-insensitive pathways, such as calcium-activated non-selective channels, cannot be excluded.

Amines↗
PubMed1989

Influence of halothane on contraction at positive membrane potentials in single cells isolated from guinea-pig ventricular muscle.

Actions of halothane were investigated under voltage-clamp conditions in single cells from guinea-pig ventricular muscle. Contraction (measured by an optical method) evoked by step depolarization to 0 mV was consistently reduced by halothane. At positive membrane potentials (+60 mV) 2% halothane did not cause a consistent depression of peak contraction, and in the majority of cells contraction was enhanced. Two per cent halothane increased the time-to-peak contraction at +60 mV. However, when a pre-pulse to 0 mV was applied to inactive calcium current through L-channels, any effect of 2% halothane on the time-to-peak of contraction was reduced or abolished. A halothane-induced increase in time-to-peak contraction was also observed at membrane potentials in the range of the action potential plateau (+20 and +40 mV). In double-pulse experiments contraction during a 'test' depolarization to +60 was measured following a 'conditioning' depolarization to 0 mV. Contraction at +60 mV was slightly reduced at brief interpulse intervals (less than 400 ms) following the 'conditioning' depolarization to 0 mV, and recovered as the interval was prolonged; in cells exposed to halothane contraction at +60 mV was no longer influenced by the interval between the pulses. Isoflurane (3.2%) had qualitatively similar but less potent effects than halothane on contraction at +60 mV. These observations are consistent with the suggestion that mechanisms for calcium entry may vary with the membrane potential: at 0 mV, the major pathway for calcium entry may be through halothane-sensitive L-type calcium channels, while at +60 mV entry may be through additional pathways which are relatively resistant to halothane. Actions of halothane on the time-to-peak of contraction may be accounted for by its influence on the sarcoplasmic reticulum to decrease net uptake and release of calcium. These actions of halothane might be of importance during the action potential plateau.

Animals↗
PubMed1989

Mechanism of potentiation of contraction by depolarization during action potentials in guinea-pig ventricular muscle.

Action potentials were recorded from guinea-pig ventricular cells and contraction recorded by an optical technique. When the plateau of a single action potential was depolarized (by 70-120 pA applied 100 ms after the upstroke for 100 ms), contraction associated with the following normal action potential was potentiated. This potentiation was not seen in cells exposed to 10 mM-caffeine. The observations are consistent with potentiation of subsequent contraction by increased loading of caffeine-sensitive calcium stores, as a consequence of reduced Ca2+ extrusion or possibly Ca2+ entry via Na+-Ca2+ exchange during a depolarized plateau.

Action Potentials↗
PubMed1988

Isoflurane depresses membrane currents associated with contraction in myocytes isolated from guinea-pig ventricle.

The influence of isoflurane on membrane currents, action potentials, and contraction was investigated in single cells isolated from guinea-pig ventricle. Isoflurane (1.65-4.45%) reduced the action potential duration at 20% and 90% repolarization times. When step depolarizations were applied under voltage-clamp conditions, there was a depression by isoflurane both of the second inward (calcium) current and of the contraction (measured by an optical method). Isoflurane also depressed "tail" currents, which were recorded on repolarization following a voltage-clamp step to 0 mV and which are thought to be activated by cytosolic calcium. Additional actions of isoflurane were investigated using a paired-pulse protocol. The observations were consistent with a reduction by isoflurane of calcium release. This action together with the reduction of calcium influx during the second inward current would contribute to the negative inotropic effect of isoflurane.

Action Potentials↗