The sodium-driven chloride/bicarbonate exchanger NDCBE in rat brain is upregulated by chronic metabolic acidosis

Acid extruders in neurons prohibit intracellular pH from falling very far below normal. Our recent report suggests that the acid-extruding sodium/bicarbonate transporter NBCn1 (Slc4a7) in rat brain is upregulated by chronic metabolic acidosis. In this study, we examined whether the Na(+)-driven Cl/HCO(3) exchanger NDCBE (Slc4a8) is also upregulated by similar systemic acid loads. Immunoblot revealed NDCBE protein (130 kDa) expressed in a variety of rat brain regions. In the hippocampus, NDCBE was localized to CA1-CA4 pyramidal neurons and dentate gyrus granular neurons determined by immunoperoxidase immunohistochemistry. The staining was dispersed in cell bodies and dendrites. NDCBE protein expression was then compared between rats in chronic metabolic acidosis and control rats. Immunoblot of crude plasma membrane fractions from the hippocampus showed a slight increase in NDCBE in acidotic rats (p=0.05). However, the expression in CA3 pyramidal neurons was significantly increased, determined by immunohistochemistry and quantitative analysis. The increase was also observed in other neurons including entorhinal cortical neurons, posterior cortical neurons, and outer stellate cells in cerebellum. The staining in choroid plexus epithelia was unaffected by chronic metabolic acidosis. These data demonstrate that the Na(+)-driven Cl/HCO(3) exchanger NDCBE is upregulated by chronic acid loads in a cell-specific manner.