Segmental differences in Slc26a3-dependent Cl^- absorption and HCO₃^- secretion in the mouse large intestine in vitro...

The anion exchanger slc26a3 (DRA), which is mutated in congenital chloride-losing diarrhea, is expressed in the apical membrane of the cecum and middle-distal colon but not in the proximal colon of rodent large intestines. To elucidate the functional roles of DRA, we measured unidirectional ³⁶Cl^- and ²²Na⁺ fluxes and HCO₃^- secretion in vitro in each of these segments using DRA-KO mice. Robust Cl^- absorption, which was largely abolished after DRA deficiency, was present in the cecum and middle-distal colon but absent in the proximal colon. Na⁺ absorption was present in all three segments in both the control and DRA-KO mice. The luminal-Cl^--dependent HCO₃^- secretions in the cecum and middle-distal colon were abolished in the DRA-KO mice. In conclusion, DRA mediates Cl^- absorption and HCO₃^- secretion in the mouse cecum and middle-distal colon, and may have roles in H₂O absorption and luminal acid/base regulation in these segments.