"Run-down" of gamma-aminobutyric acidA receptor function during whole-cell recording: a possible role for phosphorylation.
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.
Gyenes
M
M
Department of Anatomy and Cell Biology, State University of New York, Brooklyn 11203.
Farrant
M
M
Farb
D H
DH
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002642:Chick Embryo; D046508:Culture Techniques; D003956:Dialysis; D018756:GABA Antagonists; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate