Identification and expression of a unique neonatal variant of the GABA_A 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 α₃ subunit which appears unique to the developing brain, referred to here as the GABA_A receptor α₃ subunit neonatal variant (GABA_A receptor α_3N). RT-PCR and sequence analysis revealed splicing of exon 8 of the α₃ subunit. Western blot analysis showed expression of GABA_A receptor α_3N 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 α₃ and GABA_A receptor α_3N. Immunoprecipitation showed direct interaction with the GABA_A receptor subunits α₁ and γ₂ but not with gephyrin.