Comparative molecular neuroanatomy of cloned GABAA receptor subunits in the rat CNS

gamma-Aminobutyric acidA (GABAA) receptors in the mammalian central nervous system (CNS) are members of a family of ligand-gated ion channels consisting of heterooligomeric glycoprotein complexes in synaptic and extrasynaptic membranes. Although molecular cloning studies have identified 5 subunits (with approximately 40% amino acid homology) and isoforms thereof (approximately 70% homology), namely alpha 1-6, beta 1-4, gamma 1-3, delta, and rho, the subunit composition and stoichiometry of native receptors are not known. The regional distribution and cellular expression of GABAA receptor messenger RNAs (mRNAs) in the rat CNS have now been investigated by in situ hybridization histochemistry with subunit-specific 35S-labelled oligonucleotide probes on adjacent cryostat sections. Whereas alpha 1, beta 2, and gamma 2 transcripts were the most abundant and ubiquitous in the rat brain--correlating with the radioautographic distribution of GABAA receptors revealed by an ionophore ligand--others had a more restricted expression while often being abundant. For example, alpha 2 transcripts were found only in the olfactory bulb, cerebral cortex, caudate putamen, hippocampal formation, and certain lower brain stem nuclei; alpha 3 only in the olfactory bulb and cerebral cortex; alpha 5 in the hippocampal formation; and alpha 6 only in cerebellar granule cells. In addition, beta 1, beta 3, gamma 1, and delta mRNAs were also uniquely expressed in restricted brain regions. Moreover, in the spinal cord, alpha 1-3, beta 2,3, and gamma 2 mRNAs were differently expressed in Rexed layers 2-9, with alpha 2, beta 3, and gamma 2 transcripts most prominent in motoneurons of layer 9. Although differential protein trafficking could lead to the incorporation of some subunits into somatic membranes and others into dendritic membranes, some tentative conclusions as to the probable composition of native proteins in various regions of the CNS may be drawn.(ABSTRACT TRUNCATED AT 400 WORDS)