Differential expression of the Na+-Ca2+ exchanger transcripts and proteins in rat brain regions

In the central nervous system (CNS), the Na(+)-Ca(2+) exchanger plays a fundamental role in controlling the changes in the intracellular concentrations of Na(+) and Ca(2+) ions. These cations are known to regulate neurotransmitter release, cell migration and differentiation, gene expression, and neurodegenerative processes. In the present study, nonradioactive in situ hybridization and light immunohistochemistry were carried out to map the regional and cellular distribution for both transcripts and proteins encoded by the three known Na(+)-Ca(2+) exchanger genes NCX1, NCX2, and NCX3. NCX1 transcripts were particularly expressed in layers III-V of the motor cortex, in the thalamus, in CA3 and the dentate gyrus of the hippocampus, in several hypothalamic nuclei, and in the cerebellum. NCX2 transcripts were strongly expressed in all hippocampal subregions, in the striatum, and in the paraventricular thalamic nucleus. NCX3 mRNAs were mainly detected in the hippocampus, in the thalamus, in the amygdala, and in the cerebellum. Immunohistochemical analysis revealed that NCX1 protein was mainly expressed in the supragranular layers of the cerebral cortex, in the hippocampus, in the hypothalamus, in the substantia nigra and ventral tegmental area, and in the granular layer of the cerebellum. The NCX2 protein was predominantly expressed in the hippocampus, in the striatum, in the thalamus, and in the hypothalamus. The NCX3 protein was particularly found in the CA3 subregion, and in the oriens, radiatum, and lacunoso-moleculare layers of the hippocampus, in the ventral striatum, and in the cerebellar molecular layer. Collectively, these results suggest that the different Na(+)-Ca(2+) exchanger isoforms appear to be selectively expressed in several CNS regions where they might underlie different functional roles.