Background: 

HCO₃^- secretion protects the proximal duodenum against damage by gastric acid. The molecular details of basolateral HCO₃^- import are unknown, but several base im-porters are expressed in the basolateral membrane of duodenocytes. The electroneutral so-dium bicarbonate cotransporter NBCn1 (slc4a7) is expressed in the villous region of the duo-denum.

Aims: 

Genetical disruption of slc4a7 was used to determine the implication of NBCn1 in duodenocyte intracellular pH regulation and duodenal bicarbonate secretion.

Methods: 

Duodenocyte HCO₃^- uptake rates were fluorometrically assessed after acidification of intact villi and isolated duodenocytes. Basal and acid- or forskolin- stimulated secretion was measured by pH-stat titration in isolated duodenal mucosa in vitro and in the duodenum of slc4a7-/- mice and WT littermates in vivo.

Results: 

The Na⁺- and HCO₃^--dependent base uptake rate was significantly decreased in slc4a7-/- compared to wt villus duodenocytes both meas-ured in intact villi and in cell suspensions. slc4a7-/- mice displayed significantly lower basal, acid- and forskolin- stimulated duodenal HCO₃^--secretion than wt littermates in vivo. This dif-ference was larger in vivo than in isolated mucosa, and it was larger for acid- than forskolin-stimulated HCO₃^- secretion. Carbonic anhydrase-mediated CO₂ hydration played no signifi-cant role as HCO₃^- supply mechanism for basal or forskolin- stimulated secretion in the WT duodenum, but was an important alternative HCO₃^--supply mechanism in the slc4a7-/- defi-cient duodenum.

Conclusion: 

The electroneutral Na⁺ HCO₃^- cotransporter NBCn1 (slc4a7) is the major duodenal HCO₃^- importer, and is particularly important for acid-stimulated HCO₃^- secretion and, thus, likely of paramount importance for duodenal mucosal integrity.