Institut for Biomedicin

Christian Aalkjær

Essential role of the electroneutral Na+HCO3- cotransporter NBCn1 in murine duodenal acid/base balance and colonic mucus layer build-up in vivo

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  • Anurag Kumar Singh
  • ,
  • Weiliang Xia
  • ,
  • Brigitte Riederer
  • ,
  • Marina Juric
  • ,
  • Junhua Li
  • ,
  • Wen Zheng
  • ,
  • Ayhan Cinar
  • ,
  • Fang Xiao
  • ,
  • Oliver Bachmann
  • ,
  • Penghong Song
  • ,
  • Jeppe Prætorius
  • Christian Aalkjaer
  • Ursula Seidler
Duodenal epithelial cells need efficient defence strategies during gastric acidity in the lumen, while colonic mucosa counteracts damage by pathogens through the build-up of a bacteria-free adherent mucus layer. HCO(3)(-) transport is considered crucial for duodenal defence against acid as well as for mucus release and expansion, but the involved transport pathways are incompletely understood. This study investigated the significance of the electroneutral Na(+)HCO(3)(-) cotransporter NBCn1 for duodenal defence against acid and colonic mucus release. NBCn1 was localised to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells with a goblet cell predominant expression. Duodenal villous enterocyte pHi was studied before and during a luminal acid load by two-photon microscopy in exteriorised, vascularly perfused, indicator (SNARF-1 AM)-loaded duodenum of isoflurane-anaesthetised, systemic acid/base controlled mice. Acid-induced HCO(3)(-) 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 HCO(3)(-) secretory response. In the colon, mucus layer build-up was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO(3)(-) uptake is essential for optimal mucus release. The electroneutral Na(+)HCO(3)(-) cotransporter NBCn1 displays a differential cellular distribution in the murine intestine and is essential for HCO(3)(-)-dependent mucosal protective functions such as pHi-recovery and HCO(3)(-) secretion in the duodenum and mucus secretion in the colon.
TidsskriftThe Journal of Physiology
Sider (fra-til)2189-2204
StatusUdgivet - 2013

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