TY - JOUR
T1 - Inhibition of the human intermediate conductance Ca2+-activated K+ channel, hIK1, by volatile anesthetics
AU - Namba, Tsunehisa
AU - Ishii, Takahiro M.
AU - Ikeda, Mitsuko
AU - Hisano, Taizo
AU - Itoh, Tatsuya
AU - Hirota, Kiichi
AU - Adelman, John P.
AU - Fukuda, Kazuhiko
N1 - Funding Information:
This work was supported in part by Grants-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.
PY - 2000/4/28
Y1 - 2000/4/28
N2 - Ca2+-activated K+ channels (K(Ca)) regulate a wide variety of cellular functions by coupling intracellular Ca2+ concentration to membrane potential. There are three major groups of K(Ca) classified by their unit conductances: large (BK), intermediate (IK), and small (SK) conductance of channels. BK channel is gated by combined influences of Ca2+ and voltage, while IK and SK channels are gated solely by Ca2+. Volatile anesthetics inhibit BK channel activity by interfering with the Ca2+ gating mechanism. However, the effects 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 those of SK channels were not affected. The IC50 values of the volatile anesthetics, halothane, sevoflurane, enflurane, and isoflurane for hIK1 inhibition were 0.69, 0.42, 1.01 and 1.03 mM, respectively, and were in the clinically used concentration range. In contrast to BK channel, halothane inhibition of hIK1 currents was independent of Ca2+ concentration, suggesting that Ca2+ gating mechanism is not involved. These results demonstrate that volatile anesthetics, such as halothane, enflurane, isoflurane, and sevoflurane, affect BK, IK, and SK channels in distinct ways. Copyright (C) 2000.
AB - Ca2+-activated K+ channels (K(Ca)) regulate a wide variety of cellular functions by coupling intracellular Ca2+ concentration to membrane potential. There are three major groups of K(Ca) classified by their unit conductances: large (BK), intermediate (IK), and small (SK) conductance of channels. BK channel is gated by combined influences of Ca2+ and voltage, while IK and SK channels are gated solely by Ca2+. Volatile anesthetics inhibit BK channel activity by interfering with the Ca2+ gating mechanism. However, the effects 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 those of SK channels were not affected. The IC50 values of the volatile anesthetics, halothane, sevoflurane, enflurane, and isoflurane for hIK1 inhibition were 0.69, 0.42, 1.01 and 1.03 mM, respectively, and were in the clinically used concentration range. In contrast to BK channel, halothane inhibition of hIK1 currents was independent of Ca2+ concentration, suggesting that Ca2+ gating mechanism is not involved. These results demonstrate that volatile anesthetics, such as halothane, enflurane, isoflurane, and sevoflurane, affect BK, IK, and SK channels in distinct ways. Copyright (C) 2000.
KW - Anesthetic
KW - Ca-activated
KW - K channel
KW - Xenopus oocyte
KW - volatile
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U2 - 10.1016/S0014-2999(00)00254-5
DO - 10.1016/S0014-2999(00)00254-5
M3 - Article
C2 - 10794813
AN - SCOPUS:0034724660
SN - 0014-2999
VL - 395
SP - 95
EP - 101
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2
ER -