Pharmacological characterization and region-specific expression in brain of the beta 2- and beta 3-subunits of the rat GABAA receptor.
The cDNA for a third beta-subunit of the rat GABAA receptor has been cloned using another beta-subunit, which we had previously cloned [(1989) FEBS Lett. 246, 145-148], as a probe. The approximately 8-kb cDNA for this beta-subunit (termed beta 2) encodes a protein of 474 amino acid residues that shares approximately 80% sequence identity with the rat and bovine beta 1- and beta 3-subunits. Coexpression of the cloned beta-subunit cDNA with the alpha 1-subunit cDNA of the rat GABAA receptor in Xenopus oocytes produced a functional receptor and Cl- channel with pharmacological characteristics of a GABAA receptor. In contrast to interchanging alpha-subunits [(1988) Nature 335, 76-79], exchange of beta 2- or beta 3-subunits in an alpha 1/beta receptor complex did not markedly alter the pharmacological properties of expressed receptors. In situ hybridization histochemistry with synthetic subunit-specific oligo-deoxynucleotide probes revealed a region-specific expression of alpha 1-, beta 2- and beta 3-subunit mRNAs in the rat central nervous system. These observations provide an additional molecular basis for the functional heterogeneity in the GABAA receptor complex.
Lolait
S J
SJ
Laboratory of Cell biology, NIMH, Bethesda, MD 20892.
O'Carroll
A M
AM
Kusano
K
K
Mahan
L C
LC
D000818:Animals; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D015870:Gene Expression; D006651:Histocytochemistry; D015336:Molecular Probe Techniques; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000032:analysis; D009865:Oocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D014981:Xenopus / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D004247:DNA