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"Run-down" of gamma-aminobutyric acidA receptor function during whole- cell recording: a possible role for phosphorylation

M Gyenes, M Farrant and DH Farb

Department of Anatomy and Cell Biology, State University of New York, Brooklyn 11203.

When using whole-cell recording methods and a minimal intracellular medium containing only inorganic ions, ethyleneglycolbis-(beta- aminoethyl ether)-N,N,N',N'-tetraacetic acid, and N-2- hydroxyethylpiperazine-N'-2-ethanesulfonic acid, we have observed a time-dependent decrease in the responsiveness of cultured chick spinal cord neurons to gamma-aminobutyric acid (GABA). The current evoked by 30 microM GABA progressively declined to approximately 30% of its initial value after five applications at 10-min intervals. This was accompanied by an equivalent decline in the GABA-evoked membrane conductance. "Run-down" of the response was reduced when Mg2+-ATP was present in the pipet solution. Inclusion of ATP-gamma-S, an analog that donates a thiophosphate group resistant to hydrolysis, also reduced run- down. The nonhydrolyzable analog beta, gamma-imidoadenosine-5'- triphosphate was without effect. These results suggest that an ATP- dependent process, possibly phosphorylation, is involved in the maintenance of GABAA receptor function.

Volume 34, Issue 6, pp. 719-723, 12/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




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