Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function.
It is increasingly being recognized that cells coordinate the activity of separate ion channels that allow electrolytes into the cell. However, a perplexing problem in channel regulation has arisen in the fatal genetic disease cystic fibrosis, which results from the loss of a specific Cl- channel (the CFTR channel) in epithelial cell membranes. Although this defect clearly inhibits the absorption of Na+ in sweat glands, it is widely accepted that Na+ absorption is abnormally elevated in defective airways in cystic fibrosis. The only frequently cited explanation for this hypertransport is that the activity of an epithelial Na+ channel (ENaC) is inversely related to the activity of the CFTR Cl- channel. However, we report here that, in freshly isolated normal sweat ducts, ENaC activity is dependent on, and increases with, CFTR activity. Surprisingly, we also find that the primary defect in Cl- permeability in cystic fibrosis is accompanied secondarily by a Na+ conductance in this tissue that cannot be activated. Thus, reduced salt absorption in cystic fibrosis is due not only to poor Cl- conductance but also to poor Na+ conductance.
Reddy
M M
MM
Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla 92093-0831, USA.
Light
M J
MJ
Quinton
P M
PM
D000255:Adenosine Triphosphate / Q000378:metabolism; D002463:Cell Membrane Permeability; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D053503:Epithelial Sodium Channels; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D015222:Sodium Channels / Q000378:metabolism*; D012965:Sodium Chloride / Q000378:metabolism; D013545:Sweat Glands / Q000378:metabolism*
C505032:CFTR protein, human; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012965:Sodium Chloride; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases