Investigation of the abundance and subunit composition of GABAA receptor subtypes in the cerebellum of α1‐subunit‐deficient mice

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Abstract
In cerebellum, 75% of all GABAA receptors contain α1 subunits. Here, we investigated compensatory changes in GABAA receptor subunit expression and composition in α1 subunit‐knockout mice. In these mice the total number of cerebellar GABAA receptors was reduced by 46%. Whereas the number of receptors containing α6 subunits was unchanged, the total amount of α6 subunits was significantly elevated. RT‐PCR showed no increase of α6 mRNA levels, arguing against increased biosynthesis of these subunits. Elevated levels of α6 subunits in α1 ‐/‐ mice might thus have been caused by an increased incorporation of unassembled α6 subunits, replacing α1 subunits in α1α6βγ2 or α1α6βδ receptors, thus rescuing α6 subunits from degradation. Elevated levels of α3 and α4 subunits in the cerebellum of α1 ‐/‐ mice possibly can be explained similarly. Finally, a small amount of receptors containing no γ or δ subunits was identified in these mice. Results suggest a total loss of GABAA receptors in cell types where α1 was the only α subunit expressed and a partial compensation for receptor loss in cell types containing other α subunits. Our results do not support a significant compensatory synthesis of other GABAA receptor subunits in the cerebellum of α1 ‐/‐ mice.

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