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Gene Review

Slc4a7  -  solute carrier family 4, sodium...

Rattus norvegicus

Synonyms: Electroneutral sodium bicarbonate cotransporter 1, NBC-like protein, NBC3, NBCn1, Nbc, ...
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Disease relevance of Slc4a7

  • The electroneutral Na(+)-dependent HCO3- transporter NBCn1 is strongly expressed in the basolateral membrane of rat medullary thick ascending limb cells (mTAL) and is up-regulated during NH4(+)-induced metabolic acidosis [1].

High impact information on Slc4a7

  • Here we report the cloning of three variants of an electroneutral Na+/HCO3- cotransporter, NBCn1, from rat smooth muscle [2].
  • Molecular and functional characterization of the electroneutral Na/HCO3 cotransporter NBCn1 in rat hippocampal neurons [3].
  • Single-cell PCR showed that NBCn1 mRNA expression was present in both gamma-aminobutyric acid (GABA)ergic and non-GABAergic neurons [3].
  • In conclusion, NBCe in the ventricular myocyte displays considerable functional variation among the three species tested (greatest in rat, least in rabbit) and may coexist with some NBCn activity [4].
  • Anti-NBCn1 immunolabeling was confined to the basolateral plasma membrane domain of IMCD cells in the papillary two-thirds of the IM [5].

Biological context of Slc4a7


Anatomical context of Slc4a7


Associations of Slc4a7 with chemical compounds

  • Consistent with the increase in NBCn1, measurements of pH transients in medullary thick ascending limb (mTAL) cells in kidney slices revealed two- to threefold increases in DIDS- sensitive, Na(+)-dependent HCO uptake in rats with CMA [8].
  • In furosemide-induced alkalotic rats, NBCn1 protein abundance was decreased in both the IM and inner stripe of outer medulla (ISOM) as determined by immunoblotting and immunohistochemistry [5].
  • We suggest that NBCn1-mediated basolateral HCO3- influx is important for basolateral NH3 exit and thus NH4+ excretion by means of setting pHi to a more alkaline value [1].
  • Consistent with the presence of NBCn1, IMCD cells possessed stilbene-insensitive, Na(+)- and HCO(3)(-)-dependent pH recovery after acidification, as assessed by fluorescence microscopy using a pH-sensitive intracellular dye [5].
  • These results suggest that apical NBC3 and NHE3 potentially play an important role in mediating luminal H+/base transport in epididymis [9].

Analytical, diagnostic and therapeutic context of Slc4a7

  • Immunoblotting confirmed the presence of NBCn1 as an approximately 180-kDa protein of the rat IM [5].
  • Immunoelectron microscopy demonstrated that NBC3 labeling was very abundant in the apical plasma membrane, in intracellular vesicles, and in tubulocisternal profiles in the subapical domains of type A ICs [10].
  • Analysis of variable NBCn1 splicing by RT-PCR revealed that an NH2-terminal sequence, the cassette III, seems absent from cardiovascular NBCn1 and that both cassettes I and III are variable in most epithelia, whereas cassette II is absent from epithelial NBCn1 [7].
  • Furthermore, using a quantitative real-time RT-PCR (TaqMan) and Western blot analysis we demonstrated that in human cardiomyopathic hearts, mRNA and protein levels of hhNBC increase, whereas mRNA levels of the electroneutral Na(+)/HCO(3)(-) cotransporter (NBCn1) remain unchanged [11].


  1. Basolateral Na+-dependent HCO3- transporter NBCn1-mediated HCO3- influx in rat medullary thick ascending limb. Odgaard, E., Jakobsen, J.K., Frische, S., Praetorius, J., Nielsen, S., Aalkjaer, C., Leipziger, J. J. Physiol. (Lond.) (2004) [Pubmed]
  2. An electroneutral sodium/bicarbonate cotransporter NBCn1 and associated sodium channel. Choi, I., Aalkjaer, C., Boulpaep, E.L., Boron, W.F. Nature (2000) [Pubmed]
  3. Molecular and functional characterization of the electroneutral Na/HCO3 cotransporter NBCn1 in rat hippocampal neurons. Cooper, D.S., Saxena, N.C., Yang, H.S., Lee, H.J., Moring, A.G., Lee, A., Choi, I. J. Biol. Chem. (2005) [Pubmed]
  4. Functional diversity of electrogenic Na+-HCO3- cotransport in ventricular myocytes from rat, rabbit and guinea pig. Yamamoto, T., Swietach, P., Rossini, A., Loh, S.H., Vaughan-Jones, R.D., Spitzer, K.W. J. Physiol. (Lond.) (2005) [Pubmed]
  5. NBCn1 is a basolateral Na+-HCO3- cotransporter in rat kidney inner medullary collecting ducts. Praetorius, J., Kim, Y.H., Bouzinova, E.V., Frische, S., Rojek, A., Aalkjaer, C., Nielsen, S. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  6. Immunolocalization of electroneutral Na(+)-HCO cotransporters in human and rat salivary glands. Gresz, V., Kwon, T.H., Vorum, H., Zelles, T., Kurtz, I., Steward, M.C., Aalkjaer, C., Nielsen, S. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  7. An anti-NH2-terminal antibody localizes NBCn1 to heart endothelia and skeletal and vascular smooth muscle cells. Damkier, H.H., Nielsen, S., Praetorius, J. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  8. Chronic metabolic acidosis upregulates rat kidney Na-HCO cotransporters NBCn1 and NBC3 but not NBC1. Kwon, T.H., Fulton, C., Wang, W., Kurtz, I., Frøkiaer, J., Aalkjaer, C., Nielsen, S. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  9. Immunolocalization of NBC3 and NHE3 in the rat epididymis: colocalization of NBC3 and the vacuolar H+-ATPase. Pushkin, A., Clark, I., Kwon, T.H., Nielsen, S., Kurtz, I. J. Androl. (2000) [Pubmed]
  10. Immunoelectron microscopic localization of NBC3 sodium-bicarbonate cotransporter in rat kidney. Kwon, T.H., Pushkin, A., Abuladze, N., Nielsen, S., Kurtz, I. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  11. Inhibition of the cardiac electrogenic sodium bicarbonate cotransporter reduces ischemic injury. Khandoudi, N., Albadine, J., Robert, P., Krief, S., Berrebi-Bertrand, I., Martin, X., Bevensee, M.O., Boron, W.F., Bril, A. Cardiovasc. Res. (2001) [Pubmed]
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