CFTR as a cAMP-Dependent Regulator of Sodium Channels

• DOI: 10.1126/science.7543698
• Publication Date: 2006-10-27T18:19:42Z
• Authors: M. Jackson Stutts; Cecilia M. Canessa; John C. Olsen; Maura Hamrick; Jonathan A. Cohn; Bernard C. Rossier; Richard C. Boucher
• Keywords: Amiloride; Epithelial sodium channel; Cyclic adenosine monophosphate; Chloride channel

Cystic fibrosis transmembrane regulator (CFTR), the gene product that is mutated in cystic (CF) patients, has a well-recognized function as cyclic adenosine 3′,5′-monophosphate (cAMP)-regulated chloride channel, but this property does not account for abnormally high basal rate and cAMP sensitivity of sodium ion absorption CF airway epithelia. Expression complementary DNAs rat epithelial Na + channel (rENaC) alone Madin Darby canine kidney (MDCK) cells generated large amiloride-sensitive currents were stimulated by cAMP, whereas coexpression human CFTR with rENaC smaller inhibited cAMP. Parallel studies measured regulation permeability fibroblasts showed similar results. In epithelia, absence second cAMP-dependent likely accounts abnormal transport.