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Originally published In Press as doi:10.1074/jbc.M202660200 on July 15, 2002

J. Biol. Chem., Vol. 277, Issue 37, 33963-33967, September 13, 2002
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Specificity of Anion Exchange Mediated by Mouse Slc26a6*

Zhirong JiangDagger , Irina I. Grichtchenko§, Walter F. Boron§, and Peter S. AronsonDagger §

From the Departments of Dagger  Internal Medicine and of § Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8029

Recently, CFEX, the mouse orthologue of human SLC26A6, was localized to the brush border membrane of proximal tubule cells and was demonstrated to mediate Cl--formate exchange when expressed in Xenopus oocytes. The purpose of the present study was to examine whether mouse Slc26a6 can mediate one or more of the additional anion exchange processes observed to take place across the apical membrane of proximal tubule cells. Influx of [14C]formate into Slc26a6-expressing oocytes was inhibited by sulfate, oxalate, and p-aminohippurate (PAH), indicating affinity for these anions. Measurements of uptake of [14C]oxalate, [14C]PAH, and [35S]sulfate indicated that Slc26a6 can mediate transport of oxalate and sulfate but not PAH. Studies of the effect of external anions on [14C]oxalate efflux demonstrated Slc26a6-mediated Cl--oxalate, oxalate-formate, oxalate-oxalate, and oxalate-sulfate exchange. Two-electrode voltage clamp measurements indicated that Slc26a6-mediated Cl--oxalate exchange is electrogenic. Intracellular pH recordings demonstrated that Slc26a6 can mediate Cl--HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> exchange, but Cl--OH- exchange was not detected. The presence of 100 µM oxalate inhibited the rate of Cl--HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> exchange by 60%. We conclude that mouse Slc26a6 has affinity for oxalate, sulfate, and HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> in addition to Cl- and formate and can function in multiple exchange modes involving pairs of these anions. In the presence of high oxalate concentrations as found in renal tubular fluid and urine, Slc26a6 may largely function as an electrogenic Cl--oxalate exchanger.


* This work was supported by National Institutes of Health Grants DK-33793 and DK-17433.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Section of Nephrology, Dept. of Internal Medicine, Yale University School of Medicine, 333 Cedar St., LMP 2073, New Haven, CT 06520-8029. Tel.: 203-785-4186; Fax: 203-785-7068; E-mail: peter.aronson@yale.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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