Pharmacological characterization and region‐specific expression in brain of the β2‐ and β3‐subunits of the rat GABAA receptor

Abstract

The cDNA for a third β-subunit of the rat GABA_a receptor has been cloned using another β-subunit, which we had previously cloned [(1989) FEBS Lett. 246, 145-148], as a probe. The ~ 8-kb cDNA for this β-subunit (termed β2) encodes a protein of 474 amino acid residues that shares ~ 80% sequence identity with the rat and bovine β1- and β3-subunits. Coexpression of the cloned β-subunit cDNA with the α1-subunit cDNA of the rat GABA_a receptor in Xenopus oocytes produced a functional receptor and Cl⁻ channel with pharmacological characteristics of a GABA_a receptor. In contrast to interchanging α-subunits [(1988) Nature 335, 76-79], exchange of β2- or β3-subunits in α1/β receptor complex did not markedly alter the pharmacological properties of expressed receptors. In situ hybridization histochemistry with synthetic subunit-specific oligodeoxynucleotide probes revealed a region-specific expression of α1-, β2- and β3-subunit mRNAs in the rat central nervous system. These observations provide an additional molecular basis for the functional heterogeneity in the GABA_A receptor complex.