The SLC4 family of HCO3- transporters

The SLC4 family consists of ten genes. All appear to encode integral membrane proteins with very similar hydropathy plots-consistent with the presence of 10-14 transmembrane segments. At least eight SLC4 members encode proteins that transport HCO3- (or a related species, such as CO32-) across the plasma membrane. Functionally, these eight proteins fall into two major groups: three Cl-HCO3 exchangers (AE1-3) and five Na+-coupled HCO3- transporters (NBCe1, NBCe2, NBCn1, NDCBE, NCBE). Two of the Na+-coupled HCO3- transporters (NBCe1, NBCe2) are electrogenic; the other three Na+-coupled HCO3- transporters and all three AEs are electroneutral. At least NDCBE transports Cl- in addition to Na+ and HCO3-. Whether NCBE transports Cl--in addition to Na+ and HCO3--is unsettled. In addition, two other SLC4 members (AE4 and BTR1) do not yet have a firmly established function; on the basis of homology, they fall between the two major groups. A characteristic of many, though not all, SLC4 members is inhibition by 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). SLC4 gene products play important roles in the carriage of CO2 by erythrocytes, the absorption or secretion of H+ or HCO3- by several epithelia, as well as the regulation of cell volume and intracellular pH.