Identification and expression of a unique neonatal variant of the GABAA receptor α3 subunit

The GABA(A) receptor provides the majority of inhibitory neurotransmission in the adult central nervous system but in immature brain is responsible for much of the excitatory drive, a requirement for normal brain development. It is well established that GABA(A) receptor subunit expression changes across the course of brain development. In the present study, we have identified a splice variant of the GABA(A) receptor alpha(3) subunit which appears unique to the developing brain, referred to here as the GABA(A) receptor alpha(3) subunit neonatal variant (GABA(A) receptor alpha N-3). RT-PCR and sequence analysis revealed splicing of exon 8 of the alpha(3) subunit. Western blot analysis showed expression of GABA(A) receptor alpha N in the cortex of several neonatal species and significantly reduced expression of this splice variant in the corresponding adult brains. Expression was evident in multiple brain regions and decreased across development in the pig. Fractionation revealed differential cellular localisation in the parietal cortex, hippocampus and thalamus of the full-length - GABA(A) receptor alpha(3) and GABA(A) receptor alpha(3N). Immunoprecipitation showed direct interaction with the GABA(A) receptor subunits alpha(1) and alpha(2) but not with gephyrin.