A deficit of functional GABAA receptors in neurons of β3 subunit knockout mice

Mice whose gamma-aminobutyric acid type A (GABA(A)) beta(3) subunit gene is inactivated ('beta(3) knockout mice') have been previously shown to have epilepsy, hypersensitive behavior, cleft palate, and a high incidence of neonatal mortality. In this study, we analyze whole-cell responses to GABA in neurons from beta(3)(+/+), beta(3)(+/-) and beta(3)(-/-) mice. We demonstrate markedly decreased responses to GABA in both 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+ and the anticonvulsant drug loreclezole to help infer the presence of beta(2) and gamma subunits in the GABA(A) receptors remaining in neurons from beta(3)(-/-) mice. (C) 1998 Elsevier Science Ireland Ltd.