SLC26A7 is a Cl- channel regulated by intracellular pH

Kil Hwan Kim, Nikolay Shcheynikov, Youxue Wang, Shmuel Muallem

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Members of the SLC26 transporter family play an essential role in several epithelial functions, as revealed by diseases associated with mutations in members of the family. Several members were shown to function as Cl- and HCO3- transporters that likely play an important role in epithelial Cl- absorption and HCO3- secretion. However, the mechanism of most transporters is not well understood. SLC26A7 is a member of the SLC26 transporter family reported to be expressed in the baso-lateral membrane of the cortical collecting duct and parietal cells and functions as a coupled Cl-/HCO3- exchanger. In the present work we examined the transport properties of SLC26A7 to determine its transport characteristics and electrogenicity. We found that when expressed in Xenopus oocytes or HEK293 cells SLC26A7 functions as a pHi- regulated Cl- channel with minimal OH-/HCO 3- permeability. Expression of SLC26A7 in oocytes or HEK293 cells generated a Cl- current with linear I/V and an instantaneous current that was voltage-and time-independent. Based on measurement of reversal potential the selectivity of SLC26A7 is NO 3- ≫ Cl- = Br- = I- > SO42- = Glu-, although I- partially inhibited the current. Incubating the cells with HCO3 - or butyrate acidified the cytosol and increased the selectivity of SLC26A7 for Cl-. Measurement of membrane potential and pHi showed minimal OH- and HCO3- transport by SLC26A7 when the cells were incubated in Cl--containing or Cl--free media. The activity of SLC26A7 was inhibited by all inhibitors of anion transporters tested, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, diphenylamine-2-carboxylic acid, and glybenclamide. These findings reveal that SLC26A7 functions as a unique Cl- channel that is regulated by intracellular H+.

Original languageEnglish (US)
Pages (from-to)6463-6470
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number8
DOIs
StatePublished - Feb 25 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kim, K. H., Shcheynikov, N., Wang, Y., & Muallem, S. (2005). SLC26A7 is a Cl- channel regulated by intracellular pH. Journal of Biological Chemistry, 280(8), 6463-6470. https://doi.org/10.1074/jbc.M409162200