title: Generation of cAMP-activated chloride currents by expression of CFTR.
abstract: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis. In order to evaluate its function, CFTR was expressed in HeLa, Chinese hamster ovary (CHO), and NIH 3T3 fibroblast cells, and anion permeability was assessed with a fluorescence microscopic assay and the whole-cell patch-clamp technique. Adenosine 3',5'-monophosphate (cAMP) increased anion permeability and chloride currents in cells expressing CFTR, but not in cells expressing a mutant CFTR (delta F508) or in nontransfected cells. The simplest interpretation of these observations is that CFTR is itself a cAMP-activated chloride channel. The alternative interpretation, that CFTR directly or indirectly regulates chloride channels, requires that these cells have endogenous cryptic, chloride channels that are stimulated by cAMP only in the presence of CFTR.
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: M P
authors.initials: MP
authors.lastname: Anderson
authors.forename: D P
authors.initials: DP
authors.lastname: Rich
authors.forename: R J
authors.initials: RJ
authors.lastname: Gregory
authors.forename: A E
authors.initials: AE
authors.lastname: Smith
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000818:Animals; D002460:Cell Line; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D006224:Cricetinae; D000242:Cyclic AMP / Q000502:physiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D009154:Mutation; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011994:Recombinant Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP