DIFFERENTIAL EXPRESSION OF THE SHORT AND LONG FORMS OF THE GAMMA(2) SUBUNIT OF THE GABA(A) BENZODIAZEPINE RECEPTORS

The distribution of the mRNAs encoding the gamma(2S) and gamma(2L) subunits of the GABA(A) receptor in the rat brain has been revealed by in situ hybridization, northern blot and dot blot analysis using specific antisense oligonucleotides. In addition, the quantitative distribution of the gamma(2S) and gamma(2L) subunit peptides participating in the fully assembled GABA(A) receptors/benzodiazepine receptors has been mapped by immunoprecipitation with specific anti-gamma(2S) and anti-gamma(2L) antibodies. Several neuronal types and brain regions are enriched in gamma(2L) such as neurons of the layer II of striate cortex and cerebellar Purkinje cells as well as the inferior colliculus, superior colliculus, deep cerebellar nuclei, medulla and pens. Other neuronal types and regions are enriched in gamma(2S) such as the mitral cells of the olfactory bulb, pyramidal neurons of the pyriform cortex, layer VI of the neocortex, granule cells of the dentate gyrus and pyramidal cells of the hippocampus. Other cortical areas and cerebellar granule cells express both gamma(2S) and gamma(2L) in comparable amounts. There is a good correlation between the relative expression of gamma(2S) and gamma(2L) mRNAs and the relative presence of these protein subunits in fully assembled and mature receptors in the studied brain regions. The differential distribution of gamma(2S) and gamma(2L) might result in differential ethanol sensitivity of the neurons expressing these GABA(A) receptor subunits.