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1 Medicine, University of Cincinnati, Cincinnati, OH, USA
2 Physiology, University of Cincinnati, Cincinnati, OH, USA
3 Medicine, Yale University, New Haven, CT, USA
4 Physiology, Yale University, New Haven, CT, USA
5 Physiology, University of Cincinnati, Cincinnati, OH, USA; Medicine, University of Hannover, Hannover, Germany
6 Medicine, University of Cincinnati, Cincinnati, OH, USA; Research Services, Veterans Affairs Medical Center, Cincinnati, OH, USA
* To whom correspondence should be addressed. E-mail: manoocher.soleimani{at}uc.edu.
SLC26A6 (PAT1, CFEX) is an anion exchanger that is expressed on the apical membrane of kidney proximal tubule and small intestine. Modes of transport mediated by SLC26A6 include Cl-formate exchange, Cl-HCO3-, exchange and Cl-oxalate exchange. To study its role in kidney and intestine physiology, gene targeting was used to prepare mice lacking Slc26a6. Homozygous mutant Slc26a6(-/-) mice appeared healthy and exhibited normal blood pressure, kidney function and plasma electrolyte profile. In proximal tubules microperfused with a low bicarbonate-high chloride solution, the baseline rate of fluid absorption (Jv), an index of NaCl transport under these conditions, was the same in wild-type and null mice. However, the stimulation of Jv by oxalate observed in wild-type mice was completely abolished in Slc26a6 null mice (p < 0.05). Formate stimulation of Jv was partially reduced in null mice but the difference from the response in wild-type mice did not reach statistical significance. Apical membrane chloride-base exchange activity, assayed with the pH sensitive dye BCPCF in microperfused proximal tubules, was decreased by 58% in Slc26a6-/- animals (p<0.001 vs. wild types). In the duodenum, the baseline rate of bicarbonate secretion, measured in mucosal tissue mounted in Ussing chambers, was decreased by ~30% (p<0.03), whereas the forskolin-stimulated component of bicarbonate secretion was the same in wild-type and Slc26a6-/- mice. We conclude that Slc26a6 mediates oxalate-stimulated NaCl absorption and also contributes to apical membrane Cl-base exchange in the kidney proximal tubule; it also plays an important role in bicarbonate secretion in the duodenum.
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