Temperature-dependent effect of zolpidem on the GABA A receptor-mediated response at recombinant human GABA A receptor subtypes

Abstract

The effects of zolpidem on the two forms of recombinant human GABA A receptors (α1β2γ2s and α3β2γ2s) at different temperatures were functionally investigated, using the whole-cell patch recording configuration. In both forms, zolpidem potentiated the response to GABA in a concentration-dependent manner. At 16°C, the apparent dissociation constant ( K D) values for the α1β2γ2s and α3β2γ2s forms were 3.7×10 −8 and 5.6×10 −7 M, respectively. When the temperature was increased to 36°C, the K D values for the α1β2γ2s and α3β2γ2s forms were 2.1×10 −7 and 1.5×10 −6 M, respectively. Although the affinity ratio was reduced from 15.1 to 7.1-fold the selectivity of zolpidem for the α1β2γ2s still remained at 36°C.