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CFTR is restricted to a small population of high expresser cells that provide a forskolin-sensitive transepithelial Cl- conductance in the proximal colon of the possum, Trichosurus vulpecula.
MedLine Citation:
PMID:  22399668     Owner:  NLM     Status:  In-Data-Review    
The cystic fibrosis transmembrane conductance regulator (CFTR) is central to anion secretion in both the possum and eutherian small intestine. Here, we investigated its role in the possum proximal colon, which has novel transport properties compared with the eutherian proximal colon. Despite considerable CFTR expression, high doses of the CFTR activator forskolin (EC(50)≈10 μmol l(-1)) were required for a modest, CFTR-dependent increase in short-circuit current (I(sc)) in the proximal colon. Presumably, this is because CFTR is restricted to the apical membrane of a small population of CFTR high expresser (CHE) cells in the surface and upper crypt epithelium. Furthermore, although the forskolin-stimulated I(sc) was dependent on serosal Na(+), Cl(-) and HCO(3)(-), consistent with anion secretion, inhibition of the basolateral Na-K-2Cl(-) (NKCC1) or Na-HCO(3) (pNBCe1) cotransporters did not prevent it. Therefore, although NKCC1 and pNBCe1 are expressed in the colonic epithelium they do not appear to be expressed in CHE cells. At low doses (IC(50)≈1 μmol l(-1)), forskolin also decreased the transepithelial conductance (G(T)) of the colon through inhibition of a 4,4'-diisothiocyano-2,2'-stilbenedisulphonic acid-sensitive anion conductance in the basolateral membrane of the CHE cells. This conductance is arranged in series with CFTR in the CHE cells and, therefore, the CHE cells provide a transepithelial Cl(-) conductance for passive Cl(-) absorption across the epithelium. Inhibition of the basolateral Cl(-) conductance of the CHE cells by forskolin will inhibit Na(+) absorption by restricting the movement of its counter-ion Cl(-), assisting in the conversion of the tissue from an absorptive to a secretory state.
Shujun Fan; Natalie Harfoot; Ray C Bartolo; A Grant Butt
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of experimental biology     Volume:  215     ISSN:  1477-9145     ISO Abbreviation:  J. Exp. Biol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0243705     Medline TA:  J Exp Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1218-30     Citation Subset:  IM    
Department of Physiology, School of Medical Sciences, University of Otago, PO Box 913 Dunedin, New Zealand.
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