Low expression of the beta-ENaC subunit impairs lung fluid clearance in the mouse.

Détails

ID Serval
serval:BIB_CB80E793F94B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Low expression of the beta-ENaC subunit impairs lung fluid clearance in the mouse.
Périodique
American Journal of Physiology. Lung Cellular and Molecular Physiology
Auteur(s)
Randrianarison N., Clerici C., Ferreira C., Fontayne A., Pradervand S., Fowler-Jaeger N., Hummler E., Rossier B.C., Planès C.
ISSN
1040-0605
Statut éditorial
Publié
Date de publication
11/2008
Peer-reviewed
Oui
Volume
294
Numéro
3
Pages
L409-416
Langue
anglais
Résumé
Transepithelial alveolar sodium (Na+) transport mediated by the amiloride-sensitive epithelial sodium channel (ENaC) constitutes the driving force for removal of fluid from the alveolar space. To define the role of the beta-ENaC subunit in vivo in the mature lung, we studied a previously established mouse strain harboring a disruption of the beta-ENaC gene locus resulting in low levels of beta-ENaC mRNA expression. Real-time RT-PCR experiments confirmed that beta-ENaC mRNA levels were decreased by >90% in alveolar epithelial cells from homozygous mutant (m/m) mice. beta-ENaC protein was undetected in lung homogenates from m/m mice by Western blotting, but alpha- and gamma-ENaC proteins were increased by 83% and 45%, respectively, compared with wild-type (WT) mice. At baseline, Na+-driven alveolar fluid clearance (AFC) was significantly reduced by 32% in m/m mice. Amiloride at the concentration 1 mM inhibited AFC by 75% and 34% in WT and m/m mice, respectively, whereas a higher concentration (5 mM) induced a 75% inhibition of AFC in both groups. The beta2-agonist terbutaline significantly increased AFC in WT but not in m/m mice. These results show that despite the compensatory increase in alpha- and gamma-ENaC protein expression observed in mutant mouse lung, low expression of beta-ENaC results in a moderate impairment of baseline AFC and in decreased AFC sensitivity to amiloride, suggesting a possible change in the stoichiometry of ENaC channels. Finally, adequate beta-ENaC expression appears to be required for AFC stimulation by beta2-agonists.
Mots-clé
Animals, Epithelial Sodium Channel, Extravascular Lung Water, Gene Expression, Mice, Mice, Transgenic, Mutation, Protein Subunits, Pulmonary Alveoli, RNA, Messenger, Terbutaline
Pubmed
Web of science
Création de la notice
24/01/2008 14:00
Dernière modification de la notice
20/08/2019 16:46
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