Ethanol selectively blocks a noninactivating K+ current expressed in Xenopus oocytes.
There is presently a debate regarding the relative merits of lipid-based and protein-based theories of anesthesia and the action of ethanol in the central nervous system. Voltage-sensitive K+ channels play a key role as regulators of neuronal electrical activity and are potential targets of ethanol and other anesthetic agents. We investigated the action of low concentrations of ethanol on four structurally homologous cloned K+ channels expressed in Xenopus oocytes. We report that only the Drosophila Shaw2 channel, which does not inactivate upon prolonged depolarization, is rapidly and reversibly blocked by ethanol in a concentration-dependent manner (17-170 mM). The concentration dependence of the blockade can be explained by assuming a bimolecular interaction between ethanol and the channel. We also found that Shaw2 K+ channels were selectively blocked by halothane (1 mM). Our results support the "protein hypothesis" of ethanol and anesthetic action. These findings open ways to elucidate directly the molecular mechanism of interaction between general anesthetics and a voltage-sensitive K+ channel.
Covarrubias
M
M
Department of Pathology and Cell Biology, Jefferson Medical College, Philadelphia, PA 19107.
Rubin
E
E
D000758:Anesthesia; D000818:Animals; D004331:Drosophila melanogaster; D004553:Electric Conductivity; D000431:Ethanol / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes; D015221:Potassium Channels / Q000187:drug effects*; D011994:Recombinant Proteins; D014982:Xenopus laevis
D015221:Potassium Channels; D011994:Recombinant Proteins; D000431:Ethanol; D006221:Halothane