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Potentiation of the activity of the [small gamma, Greek]-aminobutyric acid type A (GABAA) receptor channel by volatile anesthetic agents is usually studied in vitro at room temperature. Systematic variation of temperature can be used to assess the relevance of this receptor to general anesthesia and to characterize the modulation of its behavior by volatile agents at normal body temperature.Potentiation of the GABAA receptor by halothane, sevoflurane, isoflurane, and methoxyflurane was studied at six temperatures in the range 10-37 [degree sign]C using the whole-cell patch-clamp technique and mouse fibroblast cells stably transfected with defined GABAA receptor subunits.Control GABA concentration-response plots showed small and physically reasonable changes in the GABA concentration required for a half-maximal effect, the Hill coefficient, and maximal response over the range 10-30 [degree sign]C. Potentiations of GABA (1 [micro sign]M) responses by aqueous minimum alveolar concentrations of the volatile anesthetic agents decreased with increasing temperature from 10-37 [degree sign]C in an agent-specific manner (methoxyflurane > isoflurane > sevoflurane > halothane) but tended to equalize at normal body temperature (37 [degree sign]C). These findings are in line with published results on the temperature dependence of anesthetic potencies in animals.These results are consistent with direct binding of volatile anesthetic agents to the GABAA receptor channel playing an important role in general anesthesia. The finding that the degree of anesthetic potentiation was agent-specific at low temperatures but not at 37 [degree sign]C emphasizes the importance of doing in vitro experiments at normal body temperature.