Voltage-dependent effects of volatile anesthetics on cardiac sodium current

Cardiac dysrhythmias during inhaled anesthesia are well documented and may, in part, involve depression of the fast inward Na+ current (I-Na) during the action potential upstroke. In this study, we examined the effects of halothane, isoflurane, and sevoflurane at clinically relevant concentrations on I-Na in single ventricular myocytes isolated enzymatically from adult guinea pig hearts. I-Na was recorded using standard whole-cell configuration of the patch clamp technique. Halothane at 0.6 mM and 1.2 mM produced significant (P < 0.05) depressions of peak I-Na of 12.3% +/- 1.8% and 24.4% +/- 4.1% (mean +/- SEM, n = 12), respectively. Isoflurane (0.5 mM, n = 12; 1.0 mM, n = 15) and sevoflurane (0.6 mM, n = 14; 1.2 mM, n = 12) were less potent than halothane, decreasing peak I-Na by 4.8% +/- 1.1% and 11.4% +/- 1.4% (isoflurane) and 3.0% +/- 0.7% and 10.7% +/- 3.9% (sevoflurane). The depressant effects on I-Na were reversible in all cases. For all anesthetics tested, the degree of block increased at more depolarizing potentials. Anesthetics induced significant shifts in the steady-state inactivation and activation of the channel toward more hyperpolarizing potentials. The present findings indicate that volatile anesthetics at clinical concentrations decrease the cardiac I-Na in a dose- and voltage-dependent manner. At approximately equianesthetic concentrations, the decrease of I-Na caused by halothane was twice that observed with isoflurane or sevoflurane.