A DEFICIT OF FUNCTIONAL GABA(A) RECEPTORS IN NEURONS OF BETA(3) SUBUNIT KNOCKOUT MICE

Mice whose gamma-aminobutyric acid type A (GABA(A)) beta(3) subunit ge ne is inactivated ('beta(3) knockout mice') have been previously shown to have epilepsy, hypersensitive behavior, cleft palate, and a high i ncidence of neonatal mortality. In this study, we analyze whole-cell r esponses to GABA in neurons from beta(3)(+/+), beta(3)(+/-) and beta(3 )(-/-) mice. We demonstrate markedly decreased responses to GABA in bo th hippocampal and dorsal root ganglion neurons isolated from beta(3)( -/-) mice without major differences in the GABA concentration-response curves. We also utilize the subunit selective pharmacology of Zn2+ an d the anticonvulsant drug loreclezole to help infer the presence of be ta(2) and gamma subunits in the GABA(A) receptors remaining in neurons from beta(3)(-/-) mice. (C) 1998 Elsevier Science Ireland Ltd.