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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 36 Cl − and 22 Na + fluxes and HCO 3 − 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 HCO 3 − secretions in the cecum and middle-distal colon were abolished in the DRA-KO mice. In conclusion, DRA mediates Cl − absorption and HCO 3 − secretion in the mouse cecum and middle-distal colon, and may have roles in H 2 O absorption and luminal acid/base regulation in these segments.

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