Background: 

Slc26a6 (PAT-1), a multi anion transporter, is strongly expressed in the apical membrane of the upper small intestine. Data on its function in the intestine are equivocal, and the stoichiometry is suggested to be 2HCO₃^-/1 Cl^-, at least when expressed in HEK cells. Aim: To investigate if, under which conditions, and by what mechanisms, Slc26a6 contributes to small intestinal fluid absorption in anesthetized mice.

Methods: 

Small intestinal fluid absorption was assessed by single pass perfusion of 3 cm long, vascularly perfused jejunal segments in 2%- isoflurane anesthetized acid/base status controlled mice with prewarmed, isotonic solutions of different ionic compositions but constant pH of 7.4.

Results: 

WT jejunum perfused with saline, pH 7.4, absorbed fluid and acidified the lumen. Slc26a3 (DRA)-deficient jejunum absorbed less fluid than WT, and acidified the lumen more strongly, consistent with its action as a Cl^-/HCO₃- exchanger. Slc26a6 (PAT-1)- deficient jejunum also absorbed less fluid, but resulted in less luminal acidification, suggesting a different function or transport mode than that of DRA. Switching the luminal solution to a 5% CO₂/HCO₃^- buffer strongly augmented fluid absorption in a PAT-1- and NHE3- but not DRA- dependent manner. Removal of luminal Na+ abolished fluid absorption in luminal NaCl but not in CO₂/HCO₃^-, where the absorption became completely dependent on PAT-1 expression. In the absence of luminal Cl^-, luminal CO₂/HCO₃^- also augumented fluid absorption, but in this case, the increase in absorption was dependent on both PAT-1 and NHE3 expression, and was markedly increased in DRA-deficient jejunum.

Conclusions: 

Slc26a6 (PAT-11) strongly augments CO₂/HCO₃- induced jejunal fluid absorption, likely operating in a 2 HCO₃^-/1 Cl^- as well as 2 HCO₃^-/1 HCO₃^-mode. Slc26a6 (PAT-1) is the first anion transporter identified to be operative in small intestinal bicarbonate absorption.