PERSISTENT ACTIVATION OF MIN-K CHANNELS BY CHEMICAL CROSS-LINKING

Expression of the structurally and functionally distinct min K channel in Xenopus oocytes results in voltage-dependent potassium currents th at activate with a characteristic slow time course. Application of a m embrane-impermeable chemical cross-linking agent to oocytes expressing min K decreased the time-dependent current, increased its rate of act ivation, and induced persistently activated inward and outward potassi um currents. These effects required membrane depolarization, demonstra ting use dependence. Persistently activated channels retained potassiu m selectivity and sensitivity to block by clofilium and barium. These results suggest that a major conformational change occurs during min K channel gating, which can be stabilized by chemical cross-linking, an d are consistent with a model in which min K channels activate by volt age-dependent subunit aggregation.