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The effect of the general anesthetic halothane on the activity of the rat skeletal muscle Ca2+-activated K+ channel in planar lipid bilayers was investigated. Halothane concentrations in the clinical range (1.0-0.2 mM) alter the regulation of the channel by both Ca2+ and membrane potential. At Ca2+ concentrations between 10 and 250 µM and membrane potentials between 0 and -30 mV, halothane significantly decreases the open state probability without changing the channel conductance. The results demonstrate that halothane can act directly on the Ca2+-activated K+ channel or its lipid environment to alter the channel Bating kinetics.