Functional expression and sites of gene transcription of a novel α subunit of the GABAAreceptor in rat brain

Two alpha subunits of the GABAA receptor in rat brain have been identified by molecular cloning. The deduced polypeptide sequences share major characteristics with other chemically gated ion channel proteins. One polypeptide represents the rat homologue of the alpha 3 subunit previously cloned from bovine brain, while the other polypeptide is a yet known subunit, termed alpha 5. When coexpressed with the beta 1 subunit in Xenopus oocytes the receptors containing the alpha 5 subunit revealed a higher sensitivity to GABA than receptors expressed from alpha 1 + beta 1 subunits or alpha 3 + beta 1 subunits (Ka = 1 microM, 13 microM and 14 microM, respectively). The alpha 5 subunit was expressed only in a few brain areas such as cerebral cortex, hippocampal formation and olfactory bulb granular layer as shown by in situ hybridization histochemistry. Since the mRNA of the alpha 5 subunit was colocalized with the alpha 1 and alpha 3 subunits only in cerebral cortex and in the hippocampal formation the alpha 5 subunit may be part of distinct GABAA receptors in neuronal populations within the olfactory bulb.