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

Background: 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 β-adrenergic channel regulation. The authors therefore studied the effects of halothane, sevoflurane, and xenon on human cardiac Ca²⁺ currents during stimulation with isoproterenol Methods: 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). Results: In the absence and in the presence of isoproterenol (1 μM), 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/o (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. Conclusions: 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.