cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
- PMID: 34610318
- DOI: 10.1016/j.celrep.2021.109795
cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
Abstract
A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na+ channel (ENaC), yielding increased Na+ reabsorption and airway dehydration. We use a non-invasive self-referencing Na+-selective microelectrode technique to measure Na+ transport across individual folds of distal airway surface epithelium preparations from CFTR-/- (CF) and wild-type (WT) swine. We show that, under unstimulated control conditions, WT and CF epithelia exhibit similar, low rates of Na+ transport that are unaffected by the ENaC blocker amiloride. However, in the presence of the cyclic AMP (cAMP)-elevating agents forskolin+IBMX (isobutylmethylxanthine), folds of WT tissues secrete large amounts of Na+, while CFTR-/- tissues absorb small, but potentially important, amounts of Na+. In cAMP-stimulated conditions, amiloride inhibits Na+ absorption in CFTR-/- tissues but does not affect secretion in WT tissues. Our results are consistent with the hypothesis that ENaC-mediated Na+ absorption may contribute to dehydration of CF distal airways.
Keywords: CF; CFTR; ENaC; airway dehydration; cystic fibrosis; distal airways.
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests The authors declare no competing interests.
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