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The Journal of Neuroscience, May 15, 2000, 20(10):3588-3595

GABA_A Receptor  and  Subunits Display Unusual Structural Variation between Species and Are Enriched in the Rat Locus Ceruleus

Saku T. Sinkkonen^{1, 2}, Michael C. Hanna³, Ewen F. Kirkness³, and Esa R. Korpi¹

¹ Department of Pharmacology and Clinical Pharmacology, and ² Turku Graduate School of Biomedical Sciences, University of Turku, FIN-20520 Turku, Finland, and ³ The Institute for Genomic Research, Rockville, Maryland 20850

Previously, GABA_A receptor  and  subunits have been identified only in human. Here, we describe properties of the  and  subunit genes from mouse and rat that reveal an unusually high level of divergence from their human homologs. In addition to a low level of amino acid sequence conservation (~70%), the rodent  subunit cDNAs encode a unique Pro/Glx motif of ~400 residues within the N-terminal extracellular domain of the subunits. Transcripts of the rat  subunit were detected in brain and heart, whereas the mouse  subunit mRNA was detectable in brain, lung, and spleen by Northern blot analysis. In situ hybridization revealed a particularly strong signal for both subunit mRNAs in rat locus ceruleus in which expression was detectable from the first postnatal day. Lower levels of coexpression were also detected in other brainstem nuclei and in the hypothalamus. However, the expression pattern of  subunit mRNA was more widespread than that of  subunit, being found also in the cerebral cortex of rat pups. In contrast to primate brain, neither subunit was expressed in the hippocampus or substantia nigra. The results indicate that GABA_A receptor  and  subunits are evolving at a much faster rate than other known GABA_A receptor subunits and that their expression patterns and functional properties may differ significantly between species.

Key words: rat GABA_A receptor subunits; subunit sequence variation; brain regional localization; locus ceruleus; hypothalamus; subunit coexpression

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20103588-08$05.00/0

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