ETHANOL SELECTIVELY BLOCKS A NONINACTIVATING K-OOCYTES( CURRENT EXPRESSED IN XENOPUS)

There is presently a debate regarding the relative merits of lipid-bas ed and protein-based theories of anesthesia and the action of ethanol in the central nervous system. Voltage-sensitive K+ channels play a ke y role as regulators of neuronal electrical activity and are potential targets of ethanol and other anesthetic agents. We investigated the a ction 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 con centration-dependent manner, (17-170 mM). The concentration dependence of the blockade can be explained by assuming a bimolecular interactio n between ethanol and the channel. We also found that Shaw2 K+ channel s were selectively blocked by halothane (1 mM). Our results support th e ''protein hypothesis'' of ethanol and anesthetic action. These findi ngs open ways to elucidate directly the molecular mechanism of interac tion between general anesthetics and a voltage-sensitive K+ channel.