Source:http://linkedlifedata.com/resource/pubmed/id/18024719
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2008-3-10
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pubmed:abstractText |
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.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epithelial Sodium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Scnn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Terbutaline
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1040-0605
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
294
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
L409-16
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pubmed:meshHeading |
pubmed-meshheading:18024719-Animals,
pubmed-meshheading:18024719-Epithelial Sodium Channel,
pubmed-meshheading:18024719-Extravascular Lung Water,
pubmed-meshheading:18024719-Gene Expression,
pubmed-meshheading:18024719-Mice,
pubmed-meshheading:18024719-Mice, Transgenic,
pubmed-meshheading:18024719-Mutation,
pubmed-meshheading:18024719-Protein Subunits,
pubmed-meshheading:18024719-Pulmonary Alveoli,
pubmed-meshheading:18024719-RNA, Messenger,
pubmed-meshheading:18024719-Terbutaline
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pubmed:year |
2008
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pubmed:articleTitle |
Low expression of the beta-ENaC subunit impairs lung fluid clearance in the mouse.
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pubmed:affiliation |
INSERM U773, CRB3, Université Denis Diderot-Paris 7, 16 rue Henri Huchard, 75018 Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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