The electroneutral Na+HCO3− cotransporter NBCn1 plays an essential role in duodenal acid/base balance and colonic mucus layer build‐up in anaestetised mice

Abstract

BackgroundDuodenal mucosa needs efficient defence strategies against gastric acidity, while colonic mucosa counteracts damage by pathogens through the build‐up of an adherent mucus layer.AimThis study delineates the significance of the electroneutral Na+HCO3− cotransporter NBCn1 (Slc4a7) for duodenal defence against acid and for colonic mucus release.Methods and ResultsNBCn1 was localised to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells. Duodenal villous enterocyte pHi was studied before and during a luminal acid load by two‐photon microscopy in exteriorised, vascularly perfused, pH indicator‐loaded duodenum of anaesthetised mice. Acid‐induced HCO3− secretion was measured in vivo by single‐pass perfusion and pH‐stat titration. After a luminal acid load, NBCn1‐deficient duodenocytes were unable to rapidly recover from intracellular acidification and could not adequately respond with a protective HCO3− secretory response. Colonic mucus layer build‐up was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO3− uptake is essential for optimal colonic mucus release.ConclusionsThe electroneutral Na+HCO3− cotransporter NBCn1 is essential for intestinal mucosal protective functions, such as pHi‐recovery and HCO3− secretion after an acid load in the duodenum, as well as mucus secretion in the colon.