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Article: Human cystic fibrosis airway epithelia have reduced Cl - conductance but not increased Na + conductance

TitleHuman cystic fibrosis airway epithelia have reduced Cl - conductance but not increased Na + conductance
Authors
KeywordsChloride secretion
Epithelial Na + channels
Issue Date2011
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 25, p. 10260-10265 How to Cite?
AbstractLoss of cystic fibrosis transmembrane conductance regulator (CFTR) anion channel function causes cystic fibrosis (CF) lung disease. CFTR is expressed in airway epithelia, but how CF alters electrolyte transport across airway epithelia has remained uncertain. Recent studies of a porcine model showed that in vivo, excised, and cultured CFTR -/- and CFTR ΔF508/ΔF508 airway epithelia lacked anion conductance, and they did not hyperabsorb Na +. Therefore, we asked whether Cl - and Na + conductances were altered in human CF airway epithelia. We studied differentiated primary cultures of tracheal/bronchial epithelia and found that transepithelial conductance (Gt) under basal conditions and the cAMP-stimulated increase in Gt were markedly attenuated in CF epithelia compared with non-CF epithelia. These data reflect loss of the CFTR anion conductance. In CF and non-CF epithelia, the Na + channel inhibitor amiloride produced similar reductions in Gt and Na + absorption, indicating that Na + conductance in CF epithelia did not exceed that in non-CF epithelia. Consistent with previous reports, adding amiloride caused greater reductions in transepithelial voltage and short-circuit current in CF epithelia than in non-CF epithelia; these changes are attributed to loss of a Cl - conductance. These results indicate that Na + conductance was not increased in these cultured CF tracheal/bronchial epithelia and point to loss of anion transport as key to airway epithelial dysfunction in CF.
Persistent Identifierhttp://hdl.handle.net/10722/137011
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Cystic Fibrosis FoundationR458-CR07
National Heart, Lung, and Blood InstituteHL51670
HL61234
National Institute of Diabetes and Digestive and Kidney DiseasesDK54759
Iowa Cardiovascular Interdisciplinary Research FellowshipHL007121
Funding Information:

We thank Tami Nesselhauf, Janice Launspach, and Theresa Mayhew for excellent assistance. We appreciate the help and assistance of the Iowa Donor Network and are deeply grateful to the persons who donated their lungs for these studies. We appreciate the valuable assistance of the University of Iowa In Vitro Models and Cell Culture Core supported in part by Grants R458-CR07 from the Cystic Fibrosis Foundation, HL51670 and HL61234 from the National Heart, Lung, and Blood Institute, and DK54759 from the National Institute of Diabetes and Digestive and Kidney Diseases. This work was supported by Grant HL51670 from the National Heart, Lung, and Blood Institute. O.A.I. was a recipient of an Iowa Cardiovascular Interdisciplinary Research Fellowship (HL007121). P. H. K. is a Research Specialist, and M.J.W. is an Investigator of The Howard Hughes Medical Institute.

References

 

DC FieldValueLanguage
dc.contributor.authorItani, OAen_HK
dc.contributor.authorChen, JHen_HK
dc.contributor.authorKarp, PHen_HK
dc.contributor.authorErnst, Sen_HK
dc.contributor.authorKeshavjee, Sen_HK
dc.contributor.authorParekh, Ken_HK
dc.contributor.authorKlesneyTait, Jen_HK
dc.contributor.authorZabner, Jen_HK
dc.contributor.authorWelsh, MJen_HK
dc.date.accessioned2011-07-29T02:14:14Z-
dc.date.available2011-07-29T02:14:14Z-
dc.date.issued2011en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2011, v. 108 n. 25, p. 10260-10265en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137011-
dc.description.abstractLoss of cystic fibrosis transmembrane conductance regulator (CFTR) anion channel function causes cystic fibrosis (CF) lung disease. CFTR is expressed in airway epithelia, but how CF alters electrolyte transport across airway epithelia has remained uncertain. Recent studies of a porcine model showed that in vivo, excised, and cultured CFTR -/- and CFTR ΔF508/ΔF508 airway epithelia lacked anion conductance, and they did not hyperabsorb Na +. Therefore, we asked whether Cl - and Na + conductances were altered in human CF airway epithelia. We studied differentiated primary cultures of tracheal/bronchial epithelia and found that transepithelial conductance (Gt) under basal conditions and the cAMP-stimulated increase in Gt were markedly attenuated in CF epithelia compared with non-CF epithelia. These data reflect loss of the CFTR anion conductance. In CF and non-CF epithelia, the Na + channel inhibitor amiloride produced similar reductions in Gt and Na + absorption, indicating that Na + conductance in CF epithelia did not exceed that in non-CF epithelia. Consistent with previous reports, adding amiloride caused greater reductions in transepithelial voltage and short-circuit current in CF epithelia than in non-CF epithelia; these changes are attributed to loss of a Cl - conductance. These results indicate that Na + conductance was not increased in these cultured CF tracheal/bronchial epithelia and point to loss of anion transport as key to airway epithelial dysfunction in CF.en_HK
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectChloride secretionen_HK
dc.subjectEpithelial Na + channelsen_HK
dc.titleHuman cystic fibrosis airway epithelia have reduced Cl - conductance but not increased Na + conductanceen_HK
dc.typeArticleen_HK
dc.identifier.emailChen, JH: jhlchen@hku.hken_HK
dc.identifier.authorityChen, JH=rp01518en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1073/pnas.1106695108en_HK
dc.identifier.pmid21646513-
dc.identifier.pmcidPMC3121869-
dc.identifier.scopuseid_2-s2.0-79959952950en_HK
dc.identifier.hkuros251309-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79959952950&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume108en_HK
dc.identifier.issue25en_HK
dc.identifier.spage10260en_HK
dc.identifier.epage10265en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000291857500049-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridItani, OA=6602163617en_HK
dc.identifier.scopusauthoridChen, JH=7501878156en_HK
dc.identifier.scopusauthoridKarp, PH=7006431484en_HK
dc.identifier.scopusauthoridErnst, S=36706048700en_HK
dc.identifier.scopusauthoridKeshavjee, S=35463592400en_HK
dc.identifier.scopusauthoridParekh, K=6701463611en_HK
dc.identifier.scopusauthoridKlesneyTait, J=6505867898en_HK
dc.identifier.scopusauthoridZabner, J=7005928925en_HK
dc.identifier.scopusauthoridWelsh, MJ=35447946600en_HK

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