Na+:HCO3- cotransporters (NBC): expression and regulation in the kidney.

Recent molecular cloning experiments have identified the existence of four NBC isoforms (NBC1, 2, 3 and 4) and two NBC-related proteins AE4 and NCBE (Anion Exchanger 4 and Sodium-dependent Chloride-Bicarbonate Exchanger). Except for AE4 which does not transport Na, all are presumed to mediate the cotransport of Na+ and HCO3-. NBC1 is expressed on the basolateral membrane of proximal tubule, is electrogenic and plays an important role in bicarbonate reabsorption in kidney proximal tubule. NBC1 is directly stimulated by carbonic anhydrase (CA) II, indicating that its inhibition by CA inhibitor acetazolamide is, in part, direct and due to the inhibition of CAII which in turn binds to the carboxy terminal tail of NBC1. NBC2 has two variants, NBCn1 and mNBC3, which are expressed in the kidney. NBCn1 is located on the basolateral membrane of the thick ascending limb of Henle whereas mNBC3 is expressed on the apical membrane of alpha intercalated cells. Both transporters are electroneutral. NBC3 or kNBC3 (also referred to as NDCBE), NBC4, AE4 and NCBE are all expressed in the kidney but their characterization is in early stages. The purpose of this article is to summarize recent functional and molecular advances on NBC isoforms and related proteins, examine the interaction of NBC1 and carbonic anhydrases, and discuss the role and regulation of NBC isoforms in renal bicarbonate transport in health and disease states.