title: Impaired cell volume regulation in intestinal crypt epithelia of cystic fibrosis mice.
abstract: Cystic fibrosis is a disease characterized by abnormalities in the epithelia of the lungs, intestine, salivary and sweat glands, liver, and reproductive systems, often as a result of inadequate hydration of their secretions. The primary defect in cystic fibrosis is the altered activity of a cAMP-activated Cl- channel, the cystic fibrosis transmembrane conductance regulator (CFTR) channel. However, it is not clear how a defect in the CFTR Cl- channel function leads to the observed pathological changes. Although much is known about the structural properties and regulation of the CFTR, little is known of its relationship to cellular functions other than the cAMP-dependent Cl- secretion. Here we report that cell volume regulation after hypotonic challenge is also defective in intestinal crypt epithelial cells isolated from CFTR -/- mutant mice. Moreover, the impairment of the regulatory volume decrease in CFTR -/- crypts appears to be related to the inability of a K+ conductance to provide a pathway for the exit of this cation during the volume adjustments. This provides evidence that the lack of CFTR protein may have additional consequences for the cellular function other than the abnormal cAMP-mediated Cl- secretion.
authors.affiliation: Nuffield Department of Clinical Biochemistry, University of Oxford, John Radcliffe Hospital, United Kingdom.
authors.forename: M A
authors.initials: MA
authors.lastname: Valverde
authors.forename: J A
authors.initials: JA
authors.lastname: O'Brien
authors.forename: F V
authors.initials: FV
authors.lastname: Sepúlveda
authors.forename: R A
authors.initials: RA
authors.lastname: Ratcliff
authors.forename: M J
authors.initials: MJ
authors.lastname: Evans
authors.forename: W H
authors.initials: WH
authors.lastname: Colledge
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D003550:Cystic Fibrosis / Q000473:pathology* / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004848:Epithelium / Q000473:pathology / Q000502:physiology; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D007413:Intestinal Mucosa / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008817:Mice, Mutant Strains; D015221:Potassium Channels / Q000502:physiology
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; D015221:Potassium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP