Background and Aims: 

Slc26a3 and a6 are members of a multi-anion transporting family and both mediate Cl-/HCO3- exchange Both play important roles in intestinal HCO3- secretion and electroneutral salt absorption, but only Slc26a6 both exports or imports HCO3- depending on pHi. Carbonic anhydrases (CA) catalyze the reversible conversion of CO2 to HCO3-, and some anion transporters form transport metabolons with CAs, to maximize the coupled catalytic/transport flux. The aim of this study was to find evidence for functional coupling and colocalization of Slc26a3 and a6 with CAII in vivo.

Methods and Results: 

The proximal duodenum of anesthetized Slc26a3, a6, CaII KO, or double KO and WT mice was perfused in situ, and basal and PG E2-stimulated HCO3- secretion was determined by back titration. Deletion of Slc26a6 slightly reduced both the basal rate and the PGE2-stimulated response, and this reduction was dramatically augmented by additional CaII ablation, which, by inself, did not have a significant effect. Similar results were obtained by luminal application of the carbonic anhydrase inhibitor methazolamide (MTZ). Slc26a3 KO duodenum displayed reduced basal HCO3-secretory rate but a normal HCO3- response to PG E2 stimulation, and MTZ did not alter either rate. CAII was found to colocalize with Slc26a6 in the apical membrane of villous enterocytes, while it had a cytoplasmic distribution in Slc26a6-deficient villi.

Conclusion: 

The anion exchanger Slc26a6, which is strongly expressed in the brush border membrane of the upper intestine, serves as an apical membrane anchor for CAII. Functional augmentation of Slc26a6 by CAII during HCO3- secretion in the murine duodenum in vivo may explain in part the strong dependency of slc26a6 HCO3- export function on the blood acid/base parameters.