GSBS Student Publications

Title

Modulation of two cloned potassium channels by 1-alkanols demonstrates different cutoffs

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Neuroscience; Department of Pharmacology and Molecular Toxicology

Date

10-6-1997

Document Type

Article

Medical Subject Headings

Alcohols; Animals; Cloning, Molecular; Dose-Response Relationship, Drug; Membrane Potentials; Oocytes; Patch-Clamp Techniques; *Potassium Channel Blockers; Potassium Channels; *Potassium Channels, Voltage-Gated; Shaw Potassium Channels; Xenopus

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Alcohol Clin Exp Res. 1997 Sep;21(6):1103-7.

Related Resources

Link to article in PubMed

Journal Title

Alcoholism, clinical and experimental research

PubMed ID

9309324