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J. Biol. Chem., Vol. 277, Issue 37, 33963-33967, September 13, 2002
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From the Departments of 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
Specificity of Anion Exchange Mediated by Mouse Slc26a6*
,
§¶
Internal Medicine and of
§ Cellular and Molecular Physiology, Yale University School
of Medicine, New Haven, Connecticut 06520-8029
-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
-OH
exchange was not detected. The
presence of 100 µM oxalate inhibited the rate of
Cl
-HCO

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.
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