Electrogenic Na+/HCO3- cotransporters: Cloning and physiology

Bicarbonate and CO2 comprise the major pH buffer of biological fluids. In t he renal proximal tubule most of the filtered HCO3- is reabsorbed by an ele ctrogenic Na/HCO3 cotransporter located at the basolateral membrane. This N a+ bicarbonate cotransporter (NBC) was recently cloned. This review highlig hts the recent developments leading to and since the cloning of NBC: NBC ex pression cloning, protein features, clone physiology, isoforms and genes, m RNA distribution, and protein distribution. With the NBC amino acid sequenc e 30-35% identical to the anion exchangers (AE1-3), a superfamily of HCO3- transporters is emerging. Physiologically, NBC is electrogenic, Na+ depende nt, HCO3- dependent, Cl- independent, and inhibited by stilbenes (DIDS and SITS). NBC clones and proteins have been isolated from several tissues (oth er than kidney) thought to have physiologically distinct HCO3- transporters . For example, NBC occurs in pancreas, prostate, brain, heart, small and la rge intestine, stomach, and epididymis. Finally, there are at least two gen es that encode NBC proteins. Possible future directions of research are dis cussed.