Backround: 

HCO₃^- secretion protects the proximal duodenum against damage by gastric acid. The molecular details of basolateral HCO₃^- import are unknown, but several base importers are expressed in the basolateral membrane of duodenocytes. The electroneutral sodium bicarbonate cotransporter NBCn1 (Slc4a7) is expressed in the villous region of the duodenum.

Aims: 

An slc4a7-/- mouse was generated and its importance for duodenal bicarbonate secretion and as well as duodenal pH_i regulation studied.

Methods: 

We measured basal as well as acid- and forskolin- stimulated HCO₃^- secretion in the proximal duodenum of anesthetized Slc4a7-/- mice and wt littermates in vivo during controlled systemic acid/base parameters, by continuous determination of the HCO₃^- that was secreted into the luminal perfusate, and in isolated duodenal mucosa in vitro in Ussing-chambers by pH-stat titration. In addition, we fluorometrically assessed base-uptake rates after acidification of intact villi and isolated duodenocytes.

Results: 

Slc4a7-/-mice displayed significantly lower basal, acid- and forskolin-stimulated duodenal HCO₃^- secretion in vivo than wt littermates. This difference was markedly larger in vivo than in isolated mucosa, and it was markedly larger for acid- than for forskolin-stimulated HCO₃^- secretion. The Na⁺- and HCO₃^--dependent base uptake rate was significantly decreased in Slc4a7-/- compared to wt villus duodenocytes both measured in the intact villus and in duodenocyte cell suspension.

Conclusion: 

The electroneutral Na⁺HCO₃^- cotransporter Slc4a7 is a major HCO₃^- importer in murine duodenum and is essential for basal and stimulated HCO₃^- secretion in vivo.