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.