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The SLC4 family of HCO3 − transporters

  • The ABC of Solute Carriers
  • Guest Editor: Matthias A. Hediger
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Abstract

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.

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Notes

  1. NBC2 lacks the amino acids encoded by exon 7. As discussed later, some authentic splice variants of NBCn1 can probably also lack exon 7. NBC2 includes both the “A” and “B” cassettes that may be present in authentic NBCn1 splice variants (see Table 3).

    Table 3 NBCn1 variants*
    Full size table

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Acknowledgements

We thank Duncan Wong for computer-related assistance. We are also grateful to Dr. Seth L. Alper for helpful discussions regarding the AE anion exchangers. Finally, we thank the members of the Romero and Boron laboratories, past and present; the experimental observations of these individuals are the basis for many of the issues discussed in this review. This work was supported by NIH grants DK-56218 (M.F.R.), HD-32573 (W.F.B.), NS-18400 (W.F.B.), and DK-30344 (W.F.B.).

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Authors and Affiliations

  1. Departments of Physiology and Biophysics and Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106–4970, USA

    Michael F. Romero

  2. Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520–8026, USA

    Christiaan M. Fulton & Walter F. Boron

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  1. Michael F. Romero
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  2. Christiaan M. Fulton
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  3. Walter F. Boron
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Correspondence to Michael F. Romero or Walter F. Boron.

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Romero, M.F., Fulton, C.M. & Boron, W.F. The SLC4 family of HCO3 − transporters. Pflugers Arch - Eur J Physiol 447, 495–509 (2004). https://doi.org/10.1007/s00424-003-1180-2

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  • DOI: https://doi.org/10.1007/s00424-003-1180-2

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