Investigation of the abundance and subunit composition of GABAA receptor subtypes in the cerebellum of alpha1-subunit-deficient mice.

In cerebellum, 75% of all GABAA receptors contain alpha1 subunits. Here, we investigated compensatory changes in GABAA receptor subunit expression and composition in alpha1 subunit-knockout mice. In these mice the total number of cerebellar GABAA receptors was reduced by 46%. Whereas the number of receptors containing alpha6 subunits was unchanged, the total amount of alpha6 subunits was significantly elevated. RT-PCR showed no increase of alpha6 mRNA levels, arguing against increased biosynthesis of these subunits. Elevated levels of alpha6 subunits in alpha1 -/- mice might thus have been caused by an increased incorporation of unassembled alpha6 subunits, replacing alpha1 subunits in alpha1alpha6betagamma2 or alpha1alpha6betadelta receptors, thus rescuing alpha6 subunits from degradation. Elevated levels of alpha3 and alpha4 subunits in the cerebellum of alpha1 -/- mice possibly can be explained similarly. Finally, a small amount of receptors containing no gamma or delta subunits was identified in these mice. Results suggest a total loss of GABAA receptors in cell types where alpha1 was the only alpha subunit expressed and a partial compensation for receptor loss in cell types containing other alpha subunits. Our results do not support a significant compensatory synthesis of other GABAA receptor subunits in the cerebellum of alpha1 -/- mice.