GABA(A)-R-α6

Abstract

GABA(A)-R-α6 is part of a large multisubunit gene family. Its gene expression is restricted to the adult cerebellar granule cells and cochlear nucleus cells, although it assembles with other subunits that are more widely expressed in the brain. This chapter presents a study in which, in α6–/– granule cells of mice, the δ subunit was selectively degraded as judged by immunoprecipitation, immunocytochemistry, and immunoblot analysis using the δ-subunit-specific antibodies. The δ subunit mRNA was present at wild-type levels in the mutant granule cells, indicating a posttranslational loss of the δ subunit. Other subunits appeared to be present at normal levels. In α6–/– neurons, the remaining α1, β2/3 and γ2 subunits could not rescue the δ subunit, indicating that certain potential subunit combinations may not be found in the wild-type cells. This study demonstrates that the α6 subunit of the GABA(A)-R is not required for normal development, viability, or fertility, nor does it appear to be a critical or unique component of the neuronal pathway mediating the hypnotic effect of ethanol and its antagonism by Ro15-4513 in mice.