title: Expression and function of the epithelial sodium channel δ-subunit in human respiratory epithelial cells in vitro.
abstract: 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.
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Panoz Institute, Dublin 2, Ireland.
authors: Elena
authors: E
authors: Schwagerus
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Panoz Institute, Dublin 2, Ireland.
authors: Svenja
authors: S
authors: Sladek
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Panoz Institute, Dublin 2, Ireland.
authors: Stephen T
authors: ST
authors: Buckley
authors: Departamento de Fisiología and Center for Biomedical Research of the Canary Islands (CIBICAN), Universidad de La Laguna, Campus de Ciencias de la Salud s/n,, 38071, La Laguna, Tenerife, Spain.
authors: Natalia
authors: N
authors: Armas-Capote
authors: Departamento de Fisiología and Center for Biomedical Research of the Canary Islands (CIBICAN), Universidad de La Laguna, Campus de Ciencias de la Salud s/n,, 38071, La Laguna, Tenerife, Spain.
authors: Diego
authors: D
authors: Alvarez de la Rosa
authors: Department of Molecular Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
authors: Brian J
authors: BJ
authors: Harvey
authors: Children's Hospital Oakland Research Institute (CHORI), Oakland, CA, 94609, USA.
authors: Horst
authors: H
authors: Fischer
authors: Children's Hospital Oakland Research Institute (CHORI), Oakland, CA, 94609, USA.
authors: Beate
authors: B
authors: Illek
authors: Department of Cardiothoracic Surgery, Völklingen Heart Centre, 66333, Völklingen, Germany.
authors: Hanno
authors: H
authors: Huwer
authors: Helmholtz Institute for Pharmaceutical Research Saarland, 66123, Saarbrücken, Germany.
authors: Nicole
authors: N
authors: Schneider-Daum
authors: Helmholtz Institute for Pharmaceutical Research Saarland, 66123, Saarbrücken, Germany.
authors: Claus-Michael
authors: CM
authors: Lehr
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Panoz Institute, Dublin 2, Ireland. ehrhardc@tcd.ie.
authors: Carsten
authors: C
authors: Ehrhardt
mesh_terms: D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005070:Evans Blue / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D061251:Primary Cell Culture; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D011744:Pyrimidinones / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
chemical_list: D004232:Diuretics; D053503:Epithelial Sodium Channels; D011744:Pyrimidinones; C507051:SCNN1D protein, human; D005070:Evans Blue; D012964:Sodium; C490483:icilin; C071423:capsazepine; D002211:Capsaicin
keywords: Airway epithelium; Alveolar epithelium; ENaC; Sodium absorption; Ussing chamber