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

The effects of zolpidem on the two forms of recombinant human GABA(A) receptors (alpha 1 beta 2 gamma 2s and alpha 3 beta 2 gamma 2s) 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 degrees C, the apparent dissociation constant (K-D) values for the alpha 1 beta 2 gamma 2s and alpha 3 beta 2 gamma 2s forms were 3.7 x 10(-8) and 5.6 x 10(-7) M, respectively. When the temperature was increased to 36 degrees C, the K-D values for the alpha 1 beta 2 gamma 2s and alpha 3 beta 2 gamma 2s forms were 2.1 x 10(-7) and 1.5 x 10(-6) M, respectively. Although the affinity ratio was reduced from 15.1 to 7.1-fold the selectivity of zolpidem for the alpha 1 beta 2 gamma 2s still remained at 36 degrees C. (C) 1998 Elsevier Science B.V. All rights reserved.