GABA(A) receptor epsilon and theta subunits display unusual structural variation between species and are enriched in the rat locus ceruleus

Previously, GABA(A) receptor epsilon and theta subunits have been identifie d only in human. Here, we describe properties of the e and theta subunit ge nes from mouse and rat that reveal an unusually high level of divergence fr om their human homologs. In addition to a low level of amino acid sequence conservation (similar to 70%), the rodent epsilon subunit cDNAs encode a un ique Pro/Glx motif of similar to 400 residues within the N-terminal extrace llular domain of the subunits. Transcripts of the rat epsilon subunit were detected in brain and heart, whereas the mouse theta subunit mRNA was detec table in brain, lung, and spleen by Northern blot analysis. In situ hybridi zation 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 nuc lei and in the hypothalamus. However, the expression pattern of theta subun it mRNA was more widespread than that of epsilon subunit, being found also in the cerebral cortex of rat pups. In contrast to primate brain, neither s ubunit was expressed in the hippocampus or substantia nigra. The results in dicate that GABA(A) receptor epsilon and theta subunits are evolving at a m uch faster rate than other known GABA(A) receptor subunits and that their e xpression patterns and functional properties may differ significantly betwe en species.