Functional and molecular properties of Na+:HCO-3 cotransporters (NBC)

Abstract

The sodium bicarbonate cotransporter (NBC) is located on the basolateral membrane of the kidney proximal tubule and is responsible for the reabsorption of the majority of filtered bicarbonate. In secretory epithelia (such as pancreatic duct) NBC is responsible for the transport of bicarbonate from the blood to the cell for the eventual secretion at the apical membrane. As such and due to its versatility, NBC can function in 2 distinct modes of bicarbonate reabsorption or secretion depending on the epithelia. NBC is also present in a wide variety of non-epithelial tissues where it is mainly involved with cell pH regulation. Recent molecular cloning experiments have identified the existence of 4 NBC isoforms (NBC1, 2, 3 and 4) and 2 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 HCO(3)-. NBC isoforms show significant homology to each other and to the AE (anion exchange) family. NBC1 shows a limited tissue expression pattern, is electrogenic and plays an important role in bicarbonate reabsorption in kidney proximal tubule. A variant of NBC1 is expressed in pancreatic duct and gastrointestinal tract, and plays an important role in HCO(3)- secretion. NBC2 and NBC3 have a wider tissue distribution than NBC1, are electroneutral, and are involved with cell pH regulation. The electrogenecity of NBC4 may be variant-specific. An NBC related protein called NCBE mediates Na-dependent, Cl-/bicarbonate ex-change. The purpose of this review is to summarize functional and molecular properties of NBC isoforms and related proteins, and discuss their role and regulation in pathophysiologic states.