Expression and function of Anoctamin 1/TMEM16A calcium-activated chloride channels in airways of in vivo mouse models for cystic fibrosis research

• Verfasst von: Hahn, Anne [VerfasserIn]
• Verfasst von: Salomon, Johanna J. [VerfasserIn]
• Verfasst von: Leitz, Dominik [VerfasserIn]
• Verfasst von: Feigenbutz, Dennis [VerfasserIn]
• Verfasst von: Korsch, Lisa [VerfasserIn]
• Verfasst von: Lisewski, Ina [VerfasserIn]
• Verfasst von: Schrimpf, Katrin [VerfasserIn]
• Verfasst von: Millar-Büchner, Pamela [VerfasserIn]
• Verfasst von: Mall, Marcus A. [VerfasserIn]
• Verfasst von: Frings, Stephan [VerfasserIn]
• Verfasst von: Möhrlen, Frank [VerfasserIn]
• Titel: Expression and function of Anoctamin 1/TMEM16A calcium-activated chloride channels in airways of in vivo mouse models for cystic fibrosis research
• Verf.angabe: Anne Hahn, Johanna J. Salomon, Dominik Leitz, Dennis Feigenbutz, Lisa Korsch, Ina Lisewski, Katrin Schrimpf, Pamela Millar-Büchner, Marcus A. Mall, Stephan Frings, Frank Möhrlen
• E-Jahr: 2018
• Jahr: 02 June 2018
• Umfang: 14 S.
• Fussnoten: Gesehen am 20.08.2019
• Titel Quelle: Enthalten in: Pflügers Archiv
• Ort Quelle: Berlin : Springer, 1868
• Jahr Quelle: 2018
• Band/Heft Quelle: 470(2018), 9, Seite 1335-1348
• ISSN Quelle: 1432-2013
• DOI: doi:10.1007/s00424-018-2160-x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Airway epithelium
• Sach-SW: Anoctamin
• Sach-SW: Chloride secretion
• Sach-SW: Cystic fibrosis
• Sach-SW: Mouse models
• Sach-SW: TMEM16A
• K10plus-PPN: 167164588X

Abstract

Physiological processes of vital importance are often safeguarded by compensatory systems that substitute for primary processes in case these are damaged by gene mutation. Ca2+-dependent Cl− secretion in airway epithelial cells may provide such a compensatory mechanism for impaired Cl− secretion via cystic fibrosis transmembrane conductance regulator (CFTR) channels in cystic fibrosis (CF). Anoctamin 1 (ANO1) Ca2+-gated Cl− channels are known to contribute to calcium-dependent Cl− secretion in tracheal and bronchial epithelia. In the present study, two mouse models of CF were examined to assess a potential protective function of Ca2+-dependent Cl− secretion, a CFTR deletion model (cftr−/−), and a CF pathology model that overexpresses the epithelial Na+ channel β-subunit (βENaC), which is encoded by the Scnn1b gene, specifically in airway epithelia (Scnn1b-Tg). The expression levels of ANO1 were examined by mRNA and protein content, and the channel protein distribution between ciliated and non-ciliated epithelial cells was analyzed. Moreover, Ussing chamber experiments were conducted to compare Ca2+-dependent Cl− secretion between wild-type animals and the two mouse models. Our results demonstrate that CFTR and ANO1 channels were co-expressed with ENaC in non-ciliated cells of mouse tracheal and bronchial epithelia. Ciliated cells did not express these proteins. Despite co-localization of CFTR and ANO1 in the same cell type, cells in cftr−/− mice displayed no altered expression of ANO1. Similarly, ANO1 expression was unaffected by βENaC overexpression in the Scnn1b-Tg line. These results suggest that the CF-related environment in the two mouse models did not induce ANO1 overexpression as a compensatory system.