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

Summary: BK channels play a counter-adaptive role in drug
tolerance and dependence
Alfredo Ghezzi, Jascha B. Pohl, Yan Wang, and Nigel S. Atkinson1
Section of Neurobiology and The Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX 78712
Edited by Howard Nash, National Institutes of Health, Bethesda, MD, and approved August 5, 2010 (received for review April 20, 2010)
Disturbance of neural activity by sedative drugs has been proposed
to trigger a homeostatic response that resists unfavorable changes
in net cellular excitability, leading to tolerance and dependence. The
Drosophila slo gene encodes a BK-type Ca2+
-activated K+
implicated in functional tolerance to alcohol and volatile anes-
thetics. We hypothesized that increased expression of BK channels
induced by these drugs constitutes the homeostatic adaptation con-
ferring resistance to sedative drugs. In contrast to the dogmatic
view that BK channels act as neural depressants, we show that
drug-induced slo expression enhances excitability by reducing the
neuronal refractory period. Although this neuroadaptation directly
counters some effects of anesthetics, it also causes long-lasting en-
hancement of seizure susceptibility, a common symptom of drug


Source: Atkinson, Nigel - Section of Neurobiology, Division of Biological Sciences, University of Texas at Austin


Collections: Biology and Medicine