We examined the cell-specific subcellular expression patterns for NKCC1, NBCe1, CFTR and NHE3 to understand the functional plasticity and synchronization of ion transport functions along the crypt-villus axis and its relevance to intestinal disease. In the unstimulated intestine, all small intestinal villus enterocytes co-expressed apical CFTR and NHE3, basolateral NBCe1, and mostly intracellular NKCC1. All (crypt and villus) goblet cells strongly expressed basolateral NKCC1 (at ~3-fold higher levels than villus enterocytes), but no CFTR, NBCe1 or NHE3. Lower crypt cells co-expressed apical CFTR and basolateral NKCC1, but no NHE3 or NBCe1 (except NBCe1-expressing proximal colonic crypts). CFTR, NBCe1 and NKCC1 co-localized with markers of early and recycling endosomes, implicating endocytic recycling in cell-specific anion transport. Brunner's glands of the proximal duodenum co-expressed high levels of apical/subapical CFTR and basolateral NKCC1, but very low levels of NBCe1, consistent with secretion of Cl- enriched fluid into the crypt. The cholinergic agonist carbachol rapidly (within 10 minutes) reduced cell volume along the entire crypt/villus axis, and promoted NHE3 internalization into early endosomes. In contrast, carbachol induced membrane recruitment of NKCC1 and CFTR in all crypt and villus enterocytes, NKCC1 in all goblet cells, and NBCe1 in all villus enterocytes. These observations support regulated vesicle traffic in Cl- secretion by goblet cells and Cl- and HCO3- secretion by villus enterocytes during the transient phase of cholinergic stimulation. Overall, the carbachol-induced membrane trafficking profile of the four ion transporters supports functional plasticity of the small intestinal villus epithelium that enables it to conduct both absorptive and secretory functions.
- cystic fibrosis transmembrane conductance regulator
- membrane trafficking
- electrogenic sodium/bicarbonate co-transporter
- sodium/proton exchanger
- pancreatic duct
- Copyright © 2010, American Journal of Physiology- Gastrointestinal and Liver Physiology