Effects of inhalational anesthetics on L-type Ca2+ currents in human atrial cardiomyocytes during beta-adrenergic stimulation.

Abstract

Anesthetics may cause cardiac side effects by their action on L-type Ca2+ channels. Direct effects on the channels have not yet been discriminated from an interference with the beta-adrenergic channel regulation. The authors therefore studied the effects of halothane, sevoflurane, and xenon on human cardiac Ca2+ currents during stimulation with isoproterenol. Currents through L-type Ca2+ channels were measured with the patch clamp technique in atrial cardiomyocytes obtained from patients undergoing cardiac surgery. Cells were superfused with solutions equilibrated with anesthetics at the desired concentrations. Ca2+ currents during pulses to 10 mV were evaluated with respect to their peak value (I(max)) and to the total moved charge (Q). In the absence and in the presence of isoproterenol (1 microm), sevoflurane (0.29 mm, 1 minimum alveolar concentration [MAC]) significantly depressed Q by 37.8 +/- 7.2% (mean +/- SD) and 40.8 +/- 10.3%, respectively. I(max) was not significantly affected in comparison with control cells never exposed to an anesthetic. Xenon (65%, 1 MAC) did not evoke significant effects. Exposure to halothane (0.39 mm, 1 MAC) during stimulation with isoproterenol significantly reduced Q by 31.3 +/- 23.3% (but not I(max)). After washout of halothane, Q was increased above the level prior to the application of halothane. Moreover, whereas Q promptly declined to baseline levels after washout of isoproterenol in controls, the previous exposure to halothane markedly delayed this decline, leaving Q significantly elevated for several minutes. Halothane exerts a dual effect on Ca2+ currents. The long-lasting stimulatory effect may contribute to the proarrhythmic potency of the drug that exceeds that of sevoflurane, which only depressed Ca2+ currents.