Microtubule Depolymerization Inhibits Ethanol-Induced Enhancement of GABAA Responses in Stably Transfected Cells |
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| Authors: | Valerie J. Whatley,Susan J. Brozowski,&dagger Karen L. Hadingham,&dagger Paul J. Whiting, &Dagger R. Adron Harris |
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| Affiliation: | Department of Pharmacology, University of Colorado Health Sciences Center;; Denver Veterans Administration Medical Center, Denver, Colorado, U.S.A.;and; Merck Sharp and Dohme Research Laboratories, Harlow, Essex, England |
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| Abstract: | Abstract: We studied whether microtubule organization is important for actions of ethanol on GABAA ergic responses by testing the effects of microtubule depolymerization on ethanol enhancement of GABA action in mouse L(tk−) cells stably transfected with GABAA receptor α1β1γ2L subunits. The microtubule-disrupting agents colchicine, taxol, and vinblastine completely blocked ethanol-induced enhancement of muscimol-stimulated chloride uptake. β-Lumicolchicine, a colchicine analogue that does not disrupt microtubules, had no effect on ethanol action. Colchicine did not alter the potentiating actions of flunitrazepam or pentobarbital on muscimol-stimulated chloride uptake. Thus, colchicine specifically inhibited the potentiating action of ethanol. From these findings, we conclude that intact microtubules are required for ethanol-induced enhancement of GABAA responses and suggest that a mechanism involving microtubules produces posttranslational modifications that are necessary for ethanol sensitivity in this cell system. |
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| Keywords: | GABAA receptor Microtubules Ethanol Colchicine |
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