Specificity of anion exchange mediated by mouse Slc26a6.
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 [(14)C]formate into Slc26a6-expressing oocytes was inhibited by sulfate, oxalate, and p-aminohippurate (PAH), indicating affinity for these anions. Measurements of uptake of [(14)C]oxalate, [(14)C]PAH, and [(35)S]sulfate indicated that Slc26a6 can mediate transport of oxalate and sulfate but not PAH. Studies of the effect of external anions on [(14)C]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(3)(-) exchange, but Cl(-)-OH(-) exchange was not detected. The presence of 100 microm oxalate inhibited the rate of Cl(-)-HCO(3)(-) exchange by 60%. We conclude that mouse Slc26a6 has affinity for oxalate, sulfate, and HCO(3)(-) 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.
Jiang
Zhirong
Z
Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8029, USA.
Grichtchenko
Irina I
II
Boron
Walter F
WF
Aronson
Peter S
PS
D000818:Animals; D027321:Anion Transport Proteins / Q000502:physiology*; D017920:Antiporters / Q000235:genetics / Q000502:physiology*; D001639:Bicarbonates / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005561:Formates / Q000378:metabolism; D051379:Mice; D010070:Oxalates / Q000378:metabolism; D000076988:Sulfate Transporters; D014981:Xenopus
D027321:Anion Transport Proteins; D017920:Antiporters; D001639:Bicarbonates; D002712:Chlorides; D005561:Formates; D010070:Oxalates; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; C030544:formic acid