The SLC4 family of bicarbonate (HCO₃⁻) transporters

Mol Aspects Med. 2013 Apr-Jun;34(2-3):159-82. doi: 10.1016/j.mam.2012.10.008.


The SLC4 family consists of 10 genes (SLC4A1-5; SLC4A7-11). All encode integral membrane proteins with very similar hydropathy plots-consistent with 10-14 transmembrane segments. Nine SLC4 members encode proteins that transport HCO3(-) (or a related species, such as CO3(2-)) across the plasma membrane. Functionally, eight of these proteins fall into two major groups: three Cl-HCO3 exchangers (AE1-3) and five Na(+)-coupled HCO3(-) transporters (NBCe1, NBCe2, NBCn1, NBCn2, NDCBE). Two of the Na(+)-coupled transporters (NBCe1, NBCe2) are electrogenic; the other three Na(+)-coupled HCO3(-) transporters and all three AEs are electroneutral. In addition, two other SLC4 members (AE4, SLC4A9 and BTR1, SLC4A11) do not yet have a firmly established function. Most, though not all, SLC4 members are functionally inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). SLC4 proteins play important roles many modes of acid-base homeostasis: the carriage of CO2 by erythrocytes, the transport of H(+) or HCO3(-) by several epithelia, as well as the regulation of cell volume and intracellular pH.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Bicarbonates / metabolism*
  • Chloride-Bicarbonate Antiporters / genetics*
  • Chloride-Bicarbonate Antiporters / metabolism
  • Chloride-Bicarbonate Antiporters / physiology*
  • Erythrocytes / metabolism
  • Gene Components
  • Humans
  • Models, Molecular*
  • Multigene Family / genetics*
  • Protein Conformation*
  • Sodium-Bicarbonate Symporters / genetics*
  • Sodium-Bicarbonate Symporters / metabolism
  • Sodium-Bicarbonate Symporters / physiology*


  • Bicarbonates
  • Chloride-Bicarbonate Antiporters
  • Sodium-Bicarbonate Symporters