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

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.