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MUCOSAL BIOLOGY

PAT-1 (Slc26a6) is the predominant apical membrane Cl^–/HCO₃^– exchanger in the upper villous epithelium of the murine duodenum

Departments of ¹Biomedical Sciences and ²Veterinary Pathobiology and ³Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri; ⁴Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; and Departments of ⁵Molecular Genetics, Biochemistry, and Microbiology and ⁶Medicine, University of Cincinnati, Cincinnati, Ohio

Submitted 1 August 2006 ; accepted in final form 12 December 2006

Basal HCO₃^– secretion across the duodenum has been shown in several species to principally involve the activity of apical membrane Cl^–/HCO₃^– exchanger(s). To investigate the identity of relevant anion exchanger(s), experiments were performed using wild-type (WT) mice and mice with gene-targeted deletion of the following Cl^–/HCO₃^– exchangers localized to the apical membrane of murine duodenal villi: Slc26a3 [down-regulated in adenoma (DRA)], Slc26a6 [putative anion transporter 1 (PAT-1)], and Slc4a9 [anion exchanger 4 (AE4)]. RT-PCR of the isolated villous epithelium demonstrated PAT-1, DRA, and AE4 mRNA expression. Using the pH-sensitive dye BCECF, anion exchange rates were measured across the apical membrane of epithelial cells in the upper villus of the intact duodenal mucosa. Under basal conditions, Cl^–/HCO₃^– exchange activity was reduced by 65–80% in the PAT-1(–) duodenum, 30–40% in the DRA(–) duodenum, and <5% in the AE4(–) duodenum compared with the WT duodenum. SO₄^2–/HCO₃^– exchange was eliminated in the PAT-1(–) duodenum but was not affected in the DRA(–) and AE4(–) duodenum relative to the WT duodenum. Intracellular pH (pH_i) was reduced in the PAT-1(–) villous epithelium but increased to WT levels in the absence of CO₂/HCO₃^– or during methazolamide treatment. Further experiments under physiological conditions indicated active pH_i compensation in the PAT-1(–) villous epithelium by combined activities of Na⁺/H⁺ exchanger 1 and Cl^–-dependent transport processes at the basolateral membrane. We conclude that 1) PAT-1 is the major contributor to basal Cl^–/HCO₃^– and SO₄^2–/HCO₃^– exchange across the apical membrane and 2) PAT-1 plays a role in pH_i regulation in the upper villous epithelium of the murine duodenum.

bicarbonate secretion; intestine; cystic fibrosis transmembrane conductance regulator; Slc4; putative anion transporter 1; downregulated in adenoma; anion exhanger isoform 4

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