Premium
Microtubule Depolymerization Inhibits Ethanol‐Induced Enhancement of GABA A Responses in Stably Transfected Cells
Author(s) -
Whatley Valerie J.,
Brozowski Susan J.,
Hadingham Karen L.,
Whiting Paul J.,
Harris R. Adron
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66031318.x
Subject(s) - colchicine , microtubule , muscimol , nocodazole , ethanol , chemistry , mechanism of action , microbiology and biotechnology , pentobarbital , biophysics , transfection , gabaergic , biochemistry , gabaa receptor , cytoskeleton , biology , pharmacology , cell , in vitro , receptor , genetics , gene
We studied whether microtubule organization is important for actions of ethanol on GABA A ergic responses by testing the effects of microtubule depolymerization on ethanol enhancement of GABA action in mouse L(tk − ) cells stably transfected with GABA A receptor α 1 β 1 γ 2L 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 GABA A responses and suggest that a mechanism involving microtubules produces posttranslational modifications that are necessary for ethanol sensitivity in this cell system.