DIFFERENTIAL LOCALIZATION OF 2 ALTERNATIVELY SPLICED GABA-A RECEPTOR GAMMA-2-SUBUNIT MESSENGER-RNAS IN THE CHICK BRAIN

Two variants of the GABA(A) receptor gamma-2 subunit are known to exist, which differ by the presence (gamma-2L) or absence (gamma-2S) of eight amino acids in the presumed intracellular loop between the third and fourth membrane-spanning domains. These variants have been shown to be generated by alternative splicing of the gamma-2-subunit primary gene transcript in mouse (Kofuji et al., J. Neurochem., 56, 713-715, 1991), and in bovine and human (Whiting et al., Proc. Natl. Acad. Sci. USA, 87, 9966 - 9970, 1990) brain. We describe here the cloning, from chick (Gallus domesticus) brain, of cDNAs that encode the gamma-2L and gamma-2S subunits, and report on the regional and cellular localization of the corresponding mRNAs as revealed by in situ hybridization histochemistry with transcript-specific oligonucleotide probes. While the two transcripts are found to be colocalized throughout the chick neuroaxis, certain nuclei (for example, the nucleus isthmi, pars magnocellularis, the nucleus isthmi, pars parvocellularis, the nucleus solitarius and the paleostriatum primitivum) are found to contain predominantly either the gamma-2S- or the gamma-2L-subunit mRNA. We conclude that receptors that contain either the gamma-2S or the gamma-2L subunit occur, and that these probably have functionally different roles in the modulation of neurotransmission in the central nervous system. In addition, our data indicate that certain cells may produce both transcripts. Consequently, these will have either a single receptor subtype that contains both a gamma-2S and a gamma-2L subunit, or two receptor subtypes, one of which contains a gamma-2S subunit and the other a gamma-2L subunit.