Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Aug 30;15(9):1082.
doi: 10.3390/ph15091082.

Understanding the Physiological Role of Electroneutral Na+-Coupled HCO3- Cotransporter and Its Therapeutic Implications

Jingjing Wang  1 , Aqeela Zahra  1 , YunFu Wang  2 , Jianping Wu  1   2
Affiliations
Review

Understanding the Physiological Role of Electroneutral Na+-Coupled HCO3- Cotransporter and Its Therapeutic Implications

Jingjing Wang et al. Pharmaceuticals (Basel). .

Abstract

Acid-base homeostasis is critical for proper physiological function and pathology. The SLC4 family of HCO3- transmembrane cotransporters is one of the HCO3- transmembrane transport carriers responsible for cellular pH regulation and the uptake or secretion of HCO3- in epithelial cells. NBCn1 (SLC4A7), an electroneutral Na+/HCO3- cotransporter, is extensively expressed in several tissues and functions as a cotransporter for net acid extrusion after cellular acidification. However, the expression and activity level of NBCn1 remain elusive. In addition, NBCn1 has been involved in numerous other cellular processes such as cell volume, cell death/survival balance, transepithelial transport, as well as regulation of cell viability. This review aims to give an inclusive overview of the most recent advances in the research of NBCn1, emphasizing the basic features, regulation, and tissue-specific physiology as well as the development and application of potent inhibitors of NBCn1 transporter in cancer therapy. Research and development of targeted therapies should be carried out for NBCn1 and its associated pathways.

Keywords: Na+/HCO3− cotransporter; cancer; cardiovascular system; central nervous system; digestive system; kidneys; pH.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Transport stoichiometry of NBCs at intracellular (I) and extracellular (o) ion concentrations and membrane potentials. Note that NBCn2 and NCBE are the two alternative names suggested for SLC4A10, depending on whether the transporter mediates net Cl− transport or only Cl− self-exchange.
Figure 2
Figure 2
NBCn1 topology. The figure illustrates the predicted NBCn1 membrane topology and localization of the primary binding site, where IP3Rs binding protein released with IP3 (IRBIT) and Carbonic Anhydrase II (CAII) can enhance the activity of NBCn1.
Figure 3
Figure 3
NBCn1 protein variants. The protein sequences contain two different Nt and can be organized into different cassettes by combining variable parts.
Figure 4
Figure 4
ErbB2-dependent SLC4A7 expression regulation model. The truncated ErbB2 receptor is responsible for regulating SLC4A7 expression.
Figure 5
Figure 5
Chemical structural formula of NBCs inhibitor.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Roos A., Boron W.F. Intracellular pH. Physiol. Rev. 1981;61:296–434. doi: 10.1152/physrev.1981.61.2.296. - DOI - PubMed
    1. Wakabayashi S., Shigekawa M., Pouyssegur J. Molecular Physiology of Vertebrate Na+/H+ Exchangers. Physiol. Rev. 1997;77:51–54. doi: 10.1152/physrev.1997.77.1.51. - DOI - PubMed
    1. Romero M.F. Molecular pathophysiology of SLC4 bicarbonate transporters. Curr. Opin. Nephrol. Hypertens. 2005;14:495–501. doi: 10.1097/01.mnh.0000168333.01831.2c. - DOI - PubMed
    1. Liu Y., Yang J., Chen L.M. Structure and Function of SLC4 Family HCO3− Transporters. Front. Physiol. 2015;6:355. doi: 10.3389/fphys.2015.00355. - DOI - PMC - PubMed
    1. Wang D.K., Liu Y., Myers E.J., Guo Y.M., Xie Z.D., Jiang D.Z., Li J.M., Yang J., Liu M., Parker M.D., et al. Effects of Nt-truncation and coexpression of isolated Nt domains on the membrane trafficking of electroneutral Na+/HCO3− cotransporters. Sci. Rep. 2015;5:12241. doi: 10.1038/srep12241. - DOI - PMC - PubMed

LinkOut - more resources