Na+: HCO3- cotransporters (NBC): Cloning and characterization

The sodium bicarbonate cotransporter (NBC I) is essential for bicarbonate t ransport across plasma membranes in epithelial and nonepithelial cells. The direction of the NaHCO3 movement in secretory epithelia is opposite to tha t in reabsorptive epithelia. In secretory epithelia (such as pancreatic duc t cells) NBC is responsible for the transport of bicarbonate from blood to the cell for eventual secretion at the apical membrane. In reabsorptive epi thelia (such as kidney proximal tubule cells) NBC is responsible for the re absorption of bicarbonate from cell to the blood. In nonepithelial cells th is transporter is mainly involved with cell pH regulation. Recent molecular cloning experiments have identified the existence of four NBC isoforms (NB C1, 2, 3 and 4) and two NBC-related proteins AE4 and NCBE (Anion Exchanger 4 and Na-dependent Chloride-Bicarbonate Exchanger). All but AE4 are presume d to mediate the cotransport of Na+ and HCO3- under normal conditions and m ay be functionally altered in certain pathologic states. NBC1 shows a limit ed tissue expression pattern, is electrogenic and plays an important role i n bicarbonate reabsorption in kidney proximal tubule. In addition to the ki dney, NBC1 is expressed in pancreatic duct cells, is activated by cystic fi brosis trans membrane conductance regulator (CFTR) and plays an important r ole in HCO3- secretion. NBC2 and NBC3 have a wider tissue distribution than NBC1, are electroneutral, and are involved with cell pH regulation. The ch aracterization of NBC4 is incomplete. The NBC-related protein called NCBE m ediates Na-dependent, Cl-/Bicarbonate Exchange. The purpose of this review is to summarize recent advances on the cloning of NBC isoforms and related proteins and their role and regulation in physiologic and pathologic states .