cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2021-10-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124721012559
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author 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
author_facet 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
author_sort Xiaojie Luan
collection DOAJ
description 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.
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spelling doaj.art-92d4289f20614c0caea8785b60305bdb2022-12-21T21:26:18ZengElsevierCell Reports2211-12472021-10-01371109795cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swineXiaojie Luan0Yen Le1Santosh Jagadeeshan2Brendan Murray3James L. Carmalt4Tanya Duke5Shannon Beazley6Masako Fujiyama7Kurtis Swekla8Bridget Gray9Monique Burmester10Veronica A. Campanucci11Alan Shipley12Terry E. Machen13Julian S. Tam14Juan P. Ianowski15Department of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaAnimal Care and Research Support, Research Excellence and Innovation, University of Saskatchewan, Saskatoon, SK, CanadaAnimal Care and Research Support, Research Excellence and Innovation, University of Saskatchewan, Saskatoon, SK, CanadaAnimal Care Unit, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada; Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, CanadaApplicable Electronics, LLC, New Haven, CT, USADepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USADepartment 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, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada; Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, Canada; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124721012559ENaCCFTRcystic fibrosisCFairway dehydrationdistal airways
spellingShingle 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
cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
Cell Reports
ENaC
CFTR
cystic fibrosis
CF
airway dehydration
distal airways
title cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
title_full cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
title_fullStr cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
title_full_unstemmed cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
title_short cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
title_sort camp triggers na absorption by distal airway surface epithelium in cystic fibrosis swine
topic ENaC
CFTR
cystic fibrosis
CF
airway dehydration
distal airways
url http://www.sciencedirect.com/science/article/pii/S2211124721012559
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