title: Chloride transport in the cystic fibrosis enterocyte.
abstract: Molecular mechanisms of intestinal chloride channel regulation and potential abnormalities in electrogenic chloride secretion in intestinal epithelium from cystic fibrosis (CF) patients were investigated by a combination of Ussing chamber, vesicle transport and off-cell patch-clamp analysis. Short circuit current (Isc) measurements in normal and CF rectal biopsies provided evidence for i) a defect in the cAMP-provoked activation of chloride secretion and a (hyper)expression of cAMP-dependent potassium secretion in all CF patients examined (n = 11); ii) a defect in the carbachol-provoked chloride secretion and a (hyper)expression of carbachol-induced potassium secretion in 6/11 patients; iii) a residual (but still impaired) carbachol-induced chloride secretion in 5/11 CF patients (including 2 sibs). The latter class of CF patients appeared to consist genetically of compound heterozygotes for the major delta-F508 deletion, suggesting a correlation between the nature of the mutation in the CF gene and the severity of the chloride secretory defect in CF intestine. In our search for a regulatory function of GTP-binding (G-) proteins detected previously in the luminal membrane of rat and human intestinal epithelial cells, evidence was found for the presence of a GTP[S]-activatable- and GDP[S]-inhibitable chloride conductance in the apical membrane of rat enterocytes and human colonocytes. In excised patches of human colonocyt membranes, this G-proteine-sensitive chloride conductance was identified further as a novel type of chloride channel (20pS; inwardly rectifying) that was different from the 33pS outwardly rectifying chloride channel activatable by cAMP-dependent proteinkinase (PK-A) and voltage depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Dept of Cell Biology & Genetics, Erasmus University, Rotterdam.
authors.forename: J
authors.initials: J
authors.lastname: Bijman
authors.forename: H
authors.initials: H
authors.lastname: Veeze
authors.forename: M
authors.initials: M
authors.lastname: Kansen
authors.forename: B
authors.initials: B
authors.lastname: Tilly
authors.forename: B
authors.initials: B
authors.lastname: Scholte
authors.forename: A
authors.initials: A
authors.lastname: Hoogeveen
authors.forename: D
authors.initials: D
authors.lastname: Halley
authors.forename: M
authors.initials: M
authors.lastname: Sinaasappel
authors.forename: H
authors.initials: H
authors.lastname: de Jonge
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism*; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D019204:GTP-Binding Proteins