Pflügers Archiv - European Journal of Physiology

, Volume 467, Issue 11, pp 2257–2273 | Cite as

Expression and function of the epithelial sodium channel δ-subunit in human respiratory epithelial cells in vitro

  • Elena Schwagerus
  • Svenja Sladek
  • Stephen T. Buckley
  • Natalia Armas-Capote
  • Diego Alvarez de la Rosa
  • Brian J. Harvey
  • Horst Fischer
  • Beate Illek
  • Hanno Huwer
  • Nicole Schneider-Daum
  • Claus-Michael Lehr
  • Carsten Ehrhardt
Ion channels, receptors and transporters


Using human airway epithelial cell lines (i.e. NCI-H441 and Calu-3) as well as human alveolar epithelial type I-like (ATI) cells in primary culture, we studied the contribution of the epithelial sodium channel δ-subunit (δ-ENaC) to transepithelial sodium transport in human lung in vitro. Endogenous δ-ENaC protein was present in all three cell types tested; however, protein abundance was low, and no expression was detected in the apical cell membrane of these cells. Similarly, known modulators of δ-ENaC activity, such as capsazepine and icilin (activators) and Evans blue (inhibitor), did not show effects on short-circuit current (I SC), suggesting that δ-ENaC is not involved in the modulation of transcellular sodium absorption in NCI-H441 cell monolayers. Over-expression of δ-ENaC in NCI-H441 cells resulted in detectable protein expression in the apical cell membrane, as well as capsazepine and icilin-stimulated increases in I SC that were effectively blocked by Evans blue and that were consistent with δ-ENaC activation and inhibition, respectively. Consequently, these observations suggest that δ-ENaC expression is low in NCI-H441, Calu-3, and ATI cells and does not contribute to transepithelial sodium absorption.


Airway epithelium Alveolar epithelium ENaC Ussing chamber Sodium absorption 



The authors thank M. Hittinger for his skilful technical support during the primary cell isolation. This work was supported by an IRCSET Government of Ireland Postgraduate Scholarship in Science, Engineering and Technology (ES, STB) and the COST Actions BM1201 (CE) and BM1301 (DA and BJH). HF and BI were supported by National Heart, Lung, and Blood Institute Grant HL86323, Cystic Fibrosis Research Inc. and Elizabeth Nash Foundation.

Supplementary material

424_2015_1693_MOESM1_ESM.docx (483 kb)
ESM 1 (DOCX 482 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Elena Schwagerus
    • 1
  • Svenja Sladek
    • 1
  • Stephen T. Buckley
    • 1
  • Natalia Armas-Capote
    • 2
  • Diego Alvarez de la Rosa
    • 2
  • Brian J. Harvey
    • 3
  • Horst Fischer
    • 4
  • Beate Illek
    • 4
  • Hanno Huwer
    • 5
  • Nicole Schneider-Daum
    • 6
  • Claus-Michael Lehr
    • 6
  • Carsten Ehrhardt
    • 1
  1. 1.School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College DublinPanoz InstituteDublin 2Ireland
  2. 2.Departamento de Fisiología and Center for Biomedical Research of the Canary Islands (CIBICAN)Universidad de La LagunaLa LagunaSpain
  3. 3.Department of Molecular Medicine, Royal College of Surgeons in IrelandBeaumont HospitalDublin 9Ireland
  4. 4.Children’s Hospital Oakland Research Institute (CHORI)OaklandUSA
  5. 5.Department of Cardiothoracic SurgeryVölklingen Heart CentreVölklingenGermany
  6. 6.Helmholtz Institute for Pharmaceutical Research SaarlandSaarbrückenGermany

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