Modulation of noninactivating K+ channels in rat cerebellar granule neurons by halothane, isoflurane, and sevoflurane

Neuronal baseline K+ channels were activated by several volatile anesthetics. Whole-cell recordings from cultured cerebellar granule neurons of 7-day-old male Sprague-Dawley rats showed outward-rectifying K+ currents with a conductance of similar to1.1 +/- 0.3 nS (n = 20) at positive potentials. The channel activity was noninactivating, exhibited no voltage gating, and was insensitive to conventional K+ channel blockers. Clinically relevant concentrations of halothane (112, 224, 336, and 448 muM) dissolved in Ringer's solution increased outward currents by 29%, 50%, 63%, and 94%, respectively (n = 5; P < 0.05; analysis of variance [ANOVA]). Similar increases in currents were produced by isoflurane (274, 411, 548, and 822 muM), which increased outward currents by 22%,47%,52%, and 60%, respectively (n = 5; P < 0.05; ANOVA). Sevoflurane 518 muM increased outward currents by 225% (n = 10; P < 0.05; ANOVA). In all experiments, channel activity quickly returned to baseline levels during wash. The outward-rectifying whole-cell current-voltage curves were consistent with the properties of anesthetic-sensitive KCNK channels. These results support the idea that noninactivating baseline K+ channels are important target sites of volatile general anesthetics.