Na/HCO3 cotransporters in rat brain: Expression in glia, neurons, and choroid plexus

We studied the expression and distribution of Na/HCO3 cotransporters in rat brain using polynucleotide probes and polyclonal antibodies derived from t he electrogenic rat kidney Na/HCO3 cotransporter (rkNBC). In whole brain, w e observed a single mRNA (similar to 7.5 kb) by Northern hybridization and a major similar to 130 kDa protein by immunoblotting with a polyclonal anti serum directed against the C terminus of rkNBC. NBC mRNA and protein were p resent in cortex, brainstem-diencephalon, and cerebellum. In situ hybridiza tion revealed NBC mRNA expression throughout the CNS, with particularly hig h levels in olfactory bulb, hippocampal dentate gyrus, and cerebellum. NBC mRNA was present in glial cells (e.g., Bergmann glia of cerebellum and hipp ocampal astrocytes) and neurons (e.g., granule cells of dentate gyrus and n eurons of cortex or striatum). Double hybridization of mRNA encoding NBC an d glutamate transporter 1 (glial marker) confirmed that both glia and neuro ns express NBC. Indirect immunofluorescence microscopy demonstrated NBC pro tein throughout the CNS, particularly in hippocampus and cerebellum. Althou gh NBC mRNA was restricted to cell bodies, NBC protein was distributed diff usely, compatible with a localization in cell processes and perhaps cell bo dies. Double labeling with glial fibrillary acidic protein (astrocytic mark er), microtubule-associated protein 2 (neuronal marker), or 2',3'-cyclic mo nonucleotide 3'-phosphodiesterase (oligodendrocytic marker) demonstrated ex pression of NBC protein in specific subpopulations of both glia and neurons . Moreover, NBC protein was present in both cultured hippocampal astrocytes and cortical neurons. NBC mRNA and protein were also present in epithelial cells of choroid plexus, ependyma, and meninges. Our results are thus cons istent with multiple novel roles for Na/HCO3 cotransport in CNS physiology.