Microtubule depolymerization inhibits ethanol-induced enhancement of GABAA responses in stably transfected cells

• Published in: Journal of neurochemistry Vol. 66; no. 3; p. 1318
• Main Authors: Whatley, V J, Brozowski, S J, Hadingham, K L, Whiting, P J, Harris, R A
• Format: Journal Article
• Language: English
• Published: England 01.03.1996
• Subjects: Animals; Cattle; Cell Line; Chlorides - metabolism; Colchicine - pharmacology; Ethanol - antagonists & inhibitors; Ethanol - pharmacology; Flunitrazepam - pharmacology; Humans; Mice; Microtubules - metabolism; Muscimol - pharmacology; Pentobarbital - pharmacology; Polymers - metabolism; Receptor Aggregation - drug effects; Receptors, GABA-A - metabolism; Transfection
• ISSN: 0022-3042
• DOI: 10.1046/j.1471-4159.1996.66031318.x

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 alpha 1 beta 1 gamma 2L subunits. The microtubule-disrupting agents colchicine, taxol, and vinblastine completely blocked ethanol-induced enhancement of muscimol-stimulated chloride uptake. beta-Lumicolchicine, a colchicine analogue that does not disrupt microtubules, had no effect on ethanol action. Colchicin did not alter the potentiating actions of flunitrazeparn or pentobarbital on muscimol-stimulated chloride uptakes. 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.