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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/L409    most recent 00307.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Randrianarison, N. Articles by Planès, C. Search for Related Content PubMed PubMed Citation Articles by Randrianarison, N. Articles by Planès, C.

EDITORIAL FOCUS

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

¹Institut National de la Santé et de la Recherche Médicale U773, CRB3, ²Université Denis Diderot-Paris 7 and ³IFR02, Université Denis Diderot-Paris 7, Paris, France; ⁴Département de Pharmacologie et de Toxicologie, Université de Lausanne, Lausanne, Switzerland; and ⁵Université de Versailles Saint-Quentin, Versailles, France

Submitted 2 August 2007 ; accepted in final form 15 November 2007

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 β-ENaC subunit in vivo in the mature lung, we studied a previously established mouse strain harboring a disruption of the β-ENaC gene locus resulting in low levels of β-ENaC mRNA expression. Real-time RT-PCR experiments confirmed that β-ENaC mRNA levels were decreased by >90% in alveolar epithelial cells from homozygous mutant (m/m) mice. β-ENaC protein was undetected in lung homogenates from m/m mice by Western blotting, but - and -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 β₂-agonist terbutaline significantly increased AFC in WT but not in m/m mice. These results show that despite the compensatory increase in - and -ENaC protein expression observed in mutant mouse lung, low expression of β-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 β-ENaC expression appears to be required for AFC stimulation by β₂-agonists.

pneumocytes; alveolar sodium transport; amiloride; cation channels

This article has been cited by other articles:

				H. G. Folkesson Variations in ENaC subunit composition may determine amiloride sensitivity and {beta}-adrenergic stimulation of lung fluid absorption Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L399 - L400. [Full Text] [PDF]