Carbachol-induced colonic mucus formation requires transport via NKCC1, K+ channels and CFTR
Pfluegers Archiv: European journal of physiology , Volume 467 - Issue 7 p. 1403- 1415
The colonic mucosa protects itself from the luminal content by secreting mucus that keeps the bacteria at a distance from the epithelium. For this barrier to be effective, the mucus has to be constantly replenished which involves exocytosis and expansion of the secreted mucins. Mechanisms involved in regulation of mucus exocytosis and expansion are poorly understood, and the aim of this study was to investigate whether epithelial anion secretion regulates mucus formation in the colon. The muscarinic agonist carbachol was used to induce parallel secretion of anions and mucus, and by using established inhibitors of ion transport, we studied how inhibition of epithelial transport affected mucus formation in mouse colon. Anion secretion and mucin exocytosis were measured by changes in membrane current and epithelial capacitance, respectively. Mucus thickness measurements were used to determine the carbachol effect on mucus growth. The results showed that the carbachol-induced increase in membrane current was dependent on NKCC1 co-transport, basolateral K+ channels and Cftr activity. In contrast, the carbachol-induced increase in capacitance was partially dependent on NKCC1 and K+ channel activity, but did not require Cftr activity. Carbachol also induced an increase in mucus thickness that was inhibited by the NKCC1 blocker bumetanide. However, mice that lacked a functional Cftr channel did not respond to carbachol with an increase in mucus thickness, suggesting that carbachol-induced mucin expansion requires Cftr channel activity. In conclusion, these findings suggest that colonic epithelial transport regulates mucus formation by affecting both exocytosis and expansion of the mucin molecules.
|Anion secretion, Capacitance, Cftr, Colon, Exocytosis, Mucus|
|Pfluegers Archiv: European journal of physiology|
|Organisation||Biophysical Genomics, Department Cell Biology & Genetics|
Gustafsson, J.K, Lindén, S.K, Alwan, A.H, Scholte, B.J, Hansson, G.C, & Sjövall, H. (2015). Carbachol-induced colonic mucus formation requires transport via NKCC1, K+ channels and CFTR. Pfluegers Archiv: European journal of physiology, 467(7), 1403–1415. doi:10.1007/s00424-014-1595-y