Inhibition of the human intermediate conductance Ca2+-activated K+ channel, hIK1, by volatile anesthetics

Ca2+-activated K+ channels (K-Ca) regulate a wide variety of cellular funct ions by coupling intracellular Ca2+ concentration to membrane potential. Th ere are three major groups of K-Ca classified by their unit conductances: l arge (BK), intermediate (IK), and small (SK) conductance of channels. BK ch annel is gated by combined influences of Ca2+ and voltage, while IK and SR channels are gated solely by Ca2+. Volatile anesthetics inhibit BK channel activity by interfering with the Ca2+ gating mechanism. However, the effect s of anesthetics on IK and SK channels are unknown. Using cloned IK and SK channels, hIK1 and hSK1-3, respectively, we found that the currents of hIK1 were inhibited rapidly and reversibly by volatile anesthetics, whereas tho se of SK channels were not affected. The IC50 values of the volatile anesth etics, halothane, sevoflurane, enflurane, and isoflurane for hIK1 inhibitio n were 0.69, 0.42, 1.01 and 1.03 mM, respectively, and were in the clinical ly used concentration range. In contrast to BK channel, halothane inhibitio n of hIK1 currents was independent of Ca2+ concentration, suggesting that C a2+ gating mechanism is not involved. These results demonstrate that volati le anesthetics, such as halothane, enflurane, isoflurane, and sevoflurane, affect BK, IK, and SK channels in distinct ways. (C) 2000 Published by Else vier Science B.V. All rights reserved.