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Modulation of Two Cloned Potassium Channels by 1‐Alkanols Demonstrates Different Cutoffs
Author(s) -
Chu Benson,
Treistman Steven N.
Publication year - 1997
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1997.tb04260.x
Subject(s) - potassium channel , potassium , modulation (music) , cloning (programming) , physics , biology , computational biology , biophysics , biological system , chemistry , computer science , acoustics , programming language , organic chemistry
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 Ca 2+ influx through endogenous voltage‐gated channels, an effect that would alter the concentration of Ca 2+ available to activate BK channels.