Science · 1995 · 1.1K citations · 26 references
Life SciencesCell BiologyMolecular BiologyCell SignalingMolecular PhysiologySignal TransductionChannelopathiesCystic FibrosisIon Channel PhysiologyIon Channel RegulationIon ChannelsSodium HomeostasisCftr Gene MutationsChloride Channel PhysiologyCyclic Adenosine Monophosphate SignalingEpithelial Sodium ChannelsSodium AbsorptionSodium Channel PhysiologySodium CotransportSodium Transport Regulation
Cystic fibrosis transmembrane regulator (CFTR), the gene product that is mutated in cystic fibrosis (CF) patients, has a well-recognized function as a cyclic adenosine 3',5'-monophosphate (cAMP)-regulated chloride channel, but this property does not account for the abnormally high basal rate and cAMP sensitivity of sodium ion absorption in CF airway epithelia. Expression of complementary DNAs for rat epithelial Na+ channel (rENaC) alone in Madin Darby canine kidney (MDCK) epithelial cells generated large amiloride-sensitive sodium currents that were stimulated by cAMP, whereas coexpression of human CFTR with rENaC generated smaller basal sodium currents that were inhibited by cAMP. Parallel studies that measured regulation of sodium permeability in fibroblasts showed similar results. In CF airway epithelia, the absence of this second function of CFTR as a cAMP-dependent regulator likely accounts for abnormal sodium transport.
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Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits
Cecilia M. Canessa, Laurent Schild, Gary Buell et al. · Nature · 1994 · 2K citations