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BK channels play a counter-adaptive role in drug tolerance and dependence

Alfredo Ghezzi1, Jascha B Pohl, Yan Wang

  • 1Section of Neurobiology and The Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX 78712, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 28, 2010
PubMed

Insights

Sedative drugs can alter neural activity, prompting a homeostatic response. In Drosophila, increased BK channels (slo gene) from drug exposure enhance excitability, contributing to tolerance and dependence.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • Sedative drugs disrupt neural activity, potentially triggering homeostatic mechanisms.
  • The Drosophila slo gene encodes BK-type Ca(2+)-activated K(+) channels, linked to tolerance to alcohol and anesthetics.

Purpose of the Study:

  • To investigate if increased BK channel expression is a homeostatic adaptation conferring resistance to sedative drugs.
  • To explore the role of BK channels in neuronal excitability and drug dependence.

Main Methods:

  • Utilized Drosophila as a model organism.
  • Examined the effects of drug-induced slo gene expression on neuronal excitability and seizure susceptibility.

Main Results:

  • Contrary to the view of BK channels as neural depressants, drug-induced slo expression enhances neuronal excitability by shortening the refractory period.
  • This neuroadaptation confers resistance to anesthetics but increases long-lasting seizure susceptibility.

Conclusions:

  • Drug-induced BK channel expression represents a homeostatic adaptation contributing to sedative drug tolerance.
  • This adaptation may explain the counter-adaptive theory of drug dependence, where tolerance mechanisms lead to withdrawal symptoms.

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