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 CO₃^2-) 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.