cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
Xiaojie Luan,
Yen Le,
Santosh Jagadeeshan,
Brendan Murray,
James L. Carmalt,
Tanya Duke,
Shannon Beazley,
Masako Fujiyama,
Kurtis Swekla,
Bridget Gray,
Monique Burmester,
Veronica A. Campanucci,
Alan Shipley,
Terry E. Machen,
Julian S. Tam,
Juan P. Ianowski
Affiliations
Xiaojie Luan
Department of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada
Yen Le
Department of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada
Santosh Jagadeeshan
Department of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada
Brendan Murray
Department of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada
James L. Carmalt
Department of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
Tanya Duke
Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
Shannon Beazley
Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
Masako Fujiyama
Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
Kurtis Swekla
Animal Care and Research Support, Research Excellence and Innovation, University of Saskatchewan, Saskatoon, SK, Canada
Bridget Gray
Animal Care and Research Support, Research Excellence and Innovation, University of Saskatchewan, Saskatoon, SK, Canada
Monique Burmester
Animal Care Unit, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada
Veronica A. Campanucci
Department of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada; Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, Canada
Alan Shipley
Applicable Electronics, LLC, New Haven, CT, USA
Terry E. Machen
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
Julian S. Tam
Department of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada; Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, Canada
Juan P. Ianowski
Department of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada; Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, Canada; Corresponding author
Summary: 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.
