Modulation of BK Channels by Ethanol

Overview

Journal Int Rev Neurobiol

Specialties Biology
Neurology
Psychiatry

Date 2016 May 31

PMID 27238266

Citations 17

Authors

A M Dopico

A N Bukiya

G Kuntamallappanavar

J Liu

Affiliations

Soon will be listed here.

Abstract

In alcohol-naïve systems, ethanol (<100mM) exposure of calcium-gated BK channels perturbs physiology and behavior. Brief (several minutes) ethanol exposure usually leads to increased BK current, which results from ethanol interaction with a pocket mapped to the BK channel-forming slo1 protein cytosolic tail domain. The importance of this region in ethanol-induced intoxication has been independently supported by an unbiased screen of Caenorhabditis elegans slo1 mutants. However, ethanol-induced BK activation is not universal as refractoriness and inhibition have been reported. The final effect depends on many factors, including intracellular calcium levels, slo1 isoform, BK beta subunit composition, posttranslational modification of BK proteins, channel lipid microenvironment, and type of ethanol administration. Studies in Drosophila melanogaster, C. elegans, and rodents show that protracted/repeated ethanol administration leads to tolerance to ethanol-induced modification of BK-driven physiology and behavior. Unveiling the mechanisms underlying tolerance is of major importance, as tolerance to ethanol has been proposed as predictor of risk for alcoholism.

Citing Articles

Hispidol Regulates Behavioral Responses to Ethanol through Modulation of BK Channels: A Novel Candidate for the Treatment of Alcohol Use Disorder.

Yang W, Goh H, Han Y, Lee M, Cha D Molecules. 2024; 29(19).

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Synaptic Mechanisms of Ethanol Tolerance and Neuroplasticity: Insights from Invertebrate Models.

Bhandari A, Seguin A, Rothenfluh A Int J Mol Sci. 2024; 25(13).

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Ethanol's interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice.

Okhuarobo A, Kreifeldt M, Gandhi P, Lopez C, Martinez B, Fleck K Mol Psychiatry. 2023; 29(2):529-542.

PMID: 38135755 PMC: 11116116. DOI: 10.1038/s41380-023-02346-y.

Forced Abstinence from Volitional Ethanol Intake Drives a Vulnerable Period of Hyperexcitability in BNST-Projecting Insular Cortex Neurons.

Taylor A, Adank D, Young P, Quan Y, Nabit B, Winder D J Neurosci. 2023; 44(4).

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Acute alcohol and chronic drinking bidirectionally regulate the excitability of prefrontal cortex vasoactive intestinal peptide interneurons.

Thompson S, Fabian C, Ferranti A, Joffe M Neuropharmacology. 2023; 238:109638.

PMID: 37482180 PMC: 10529784. DOI: 10.1016/j.neuropharm.2023.109638.

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