Chu B, Treistman S N
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical Center, Worcester 01655, USA.
Alcohol Clin Exp Res. 1997 Sep;21(6):1103-7.
It is not known whether alcohols modulate ion channels by directly binding to the channel protein or by perturbing the surrounding membrane lipid. Cutoff describes the phenomenon where the potency of 1-alkanols monotonically increases with alkyl chain length until a loss of efficacy occurs. Determination of the cutoff for a variety of channels can be important, because similar and/or dissimilar cutoffs might yield information regarding the nature of ethanol's site of action. In this study, the two-electrode voltage clamp technique was used to determine the cutoffs for the 1-alkanol potentiation of cloned Ca(2+)-activated-K+ (BK) channels and for the inhibition of cloned Shaw2 K+ channels, expressed in Xenopus oocytes. Ethanol, butanol, hexanol, and heptanol reversibly enhanced BK currents, whereas octanol and nonanol had no effect. In contrast, Shaw2 currents were potently inhibited by both octanol and decanol, but not by undecanol. Taken together, data demonstrate that the modulation of K+ channels by long chain alcohols is channel-specific. Interestingly, ethanol was a less potent activator of BK currents in the intact oocyte in comparison with its effect on this channel in excised membrane patches. The decrease in potency could not be attributed to an ethanol-dependent change in Ca2+ influx through endogenous voltage-gated channels, an effect that would alter the concentration of Ca2+ available to activate BK channels.
尚不清楚醇类是通过直接与通道蛋白结合还是通过扰动周围的膜脂来调节离子通道。截止现象描述的是，1-链烷醇的效力随烷基链长度单调增加，直至出现效力丧失的情况。确定多种通道的截止值可能很重要，因为相似和/或不同的截止值可能会提供有关乙醇作用位点性质的信息。在本研究中，采用双电极电压钳技术来确定非洲爪蟾卵母细胞中表达的克隆钙激活钾（BK）通道的1-链烷醇增强效应以及克隆的Shaw2钾通道抑制作用的截止值。乙醇、丁醇、己醇和庚醇可可逆地增强BK电流，而辛醇和壬醇则无作用。相反，Shaw2电流受到辛醇和癸醇的强烈抑制，但不受十一醇的抑制。综上所述，数据表明长链醇对钾通道的调节具有通道特异性。有趣的是，与乙醇对切除膜片上该通道的作用相比，乙醇在完整卵母细胞中对BK电流的激活作用较弱。效力的降低不能归因于通过内源性电压门控通道的钙离子内流的乙醇依赖性变化，这种效应会改变可用于激活BK通道的钙离子浓度。
