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 Guinea Pigs