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 approximately 1.1 +/- 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 micro M) 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 micro M), which increased outward currents by 22%, 47%, 52%, and 60%, respectively (n = 5; P < 0.05; ANOVA). Sevoflurane 518 micro M 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.


CONCLUSIONS
The volatile anesthetics halothane, isoflurane, and sevoflurane, reversibly enhanced a noninactivating outwardly rectifying K(+) current in rat cerebellar granule neurons. These findings support a model of anesthesia that includes a site of action at baseline K(+) channels.
Shin
Woo-Jong
WJ
Department of Anesthesia and Perioperative Care, University of California, San Francisco, California.
Winegar
Bruce D
BD
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000077149:Sevoflurane; D007530:Isoflurane; D006221:Halothane