Modulation of the GABAA receptor by propofol is independent of the gamma subunit
Jones, M.V.; Harrison, N.L.; Pritchett, D.B.; Hales, T.G.
Journal of Pharmacology and Experimental Therapeutics 274(2): 962-968
1995
ISSN/ISBN: 0022-3565 PMID: 7636760 Document Number: 444960
Many anxiolytics, anticonvulsants and general anesthetics modulate gamma-aminobutyric acid type A (GABA-A) receptors. The anxiolytic benzodiazepines potentiate the actions of GABA, and this only at GABA-A receptors with gamma subunits. The general anesthetics both potentiate GABA and activate GABA-A receptors directly, but their binding sites on the receptor are poorly defined. We examined whether the gamma-2 subunit was required for the modulation of GABA-A receptors by the general anesthetic 2,6-diisopropylphenol (propofol). Using the patch-clamp technique, we recorded membrane currents from HEK293 cells transfected with human alpha-2, beta-1 and gamma-2 cDNAs and with alpha-2 and beta-1 cDNAs alone. Both forms of the receptor were activated by GABA and by propofol at low concentrations. At maximal doses, propofol was considerably less effective than GABA as an activator of alpha-2-beta-1 GABA-A receptors, but it had an efficacy similar to that of GABA as an activator of alpha-2-beta-1-gamma-2s receptors. In addition to activating currents directly, propofol potentiated currents elicited by GABA recorded from cells expressing either subunit combination. We conclude that the gamma-2 subunit is not a prerequisite for activation of GABA-A receptors by propofol or for its potentiation of GABA-activated currents. However, the subunit may contribute to the efficacy of propofol as a GABA-A receptor activator.