CFTR as a cAMP-dependent regulator of sodium channels.
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.
Stutts
M J
MJ
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill 27599-7020, USA.
Canessa
C M
CM
Olsen
J C
JC
Hamrick
M
M
Cohn
J A
JA
Rossier
B C
BC
Boucher
R C
RC
D016475:3T3 Cells; D000042:Absorption; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability; D018118:Chloride Channels / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D018076:DNA, Complementary; D004285:Dogs; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018408:Patch-Clamp Techniques; D051381:Rats; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D014162:Transfection
C505032:CFTR protein, human; D018118:Chloride Channels; D018076:DNA, Complementary; D008565:Membrane Proteins; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; D012964:Sodium; D000242:Cyclic AMP