BK Channels: mediators and models for alcohol tolerance

Trends Neurosci. 2009 Dec;32(12):629-37. doi: 10.1016/j.tins.2009.08.001. Epub 2009 Sep 24.


Enhanced acute tolerance predicts alcohol abuse. We describe work on the role of the calcium- and voltage-gated BK channel in alcohol tolerance, highlighting the lipid environment, BK protein isoform selection and auxiliary BK channel proteins. We show how ethanol, which had the reputation of a nonspecific membrane perturbant, is now being examined at realistic concentrations with cutting-edge techniques, providing novel molecular targets for therapeutic approaches to alcoholism. Addictive disorders impact our emotional, physical and financial status, and burden our healthcare system. Although alcohol is the focus of this review, it is highly probable, given the common neural and biochemical pathways used by drugs of abuse, that the findings described here will also apply to other drugs.

Publication types

  • Review

MeSH terms

  • Alcohol Drinking / genetics
  • Animals
  • Drug Tolerance / genetics
  • Drug Tolerance / physiology*
  • Epigenesis, Genetic / genetics
  • Epigenesis, Genetic / physiology
  • Ethanol / pharmacology*
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channels / drug effects*
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism
  • Membrane Lipids / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / metabolism
  • Models, Molecular
  • Models, Neurological
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / physiology
  • Phosphorylation
  • Protein Isoforms / drug effects
  • Protein Isoforms / metabolism
  • Substance-Related Disorders / metabolism
  • Substance-Related Disorders / physiopathology


  • Large-Conductance Calcium-Activated Potassium Channels
  • Membrane Lipids
  • MicroRNAs
  • Protein Isoforms
  • Ethanol