Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome

Details

Serval ID
serval:BIB_97C3E12BE471
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dysfunction of the epithelial sodium channel expressed in the kidney of a mouse model for Liddle syndrome
Journal
Journal of the American Society of Nephrology
Author(s)
Pradervand  S., Vandewalle  A., Bens  M., Gautschi  I., Loffing  J., Hummler  E., Schild  L., Rossier  B. C.
ISSN
1046-6673
Publication state
Published
Issued date
09/2003
Peer-reviewed
Oui
Volume
14
Number
9
Pages
2219-28
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep
Abstract
The Liddle syndrome is a dominant form of salt-sensitive hypertension resulting from mutations in the beta or gamma subunit of ENaC. A previous study established a mouse model carrying a premature Stop codon corresponding to the R(566stop) mutation (L) found in the original pedigree that recapitulates to a large extent the human disease. This study investigated the renal Na(+) transport in vivo, ex vivo (intact perfused tubules), and in vitro (primary cultured cortical collecting ducts [CCD]). In vivo, upon 6 to 12 h of salt repletion, after 1 week of low-salt diet, the L/L mice showed a delayed urinary sodium excretion, despite a lower aldosterone secretion as compared with controls. After 6 h salt of repletion, ENaC gamma subunit is rapidly removed from the apical plasma membrane in wild-type mice, whereas it is retained at the apical membrane in L/L mice. Ex vivo, isolated perfused CCD from L/L mice exhibited higher transepithelial potential differences than perfused CCD isolated from +/+ mice. In vitro, confluent primary cultures of CCD microdissected from L/L kidneys grown on permeable filters exhibited significant lower transepithelial electrical resistance and higher negative potential differences than their cultured L/+ and +/+ CCD counterparts. The equivalent short-circuit current (I(eq)) and the amiloride-sensitive I(eq) was approximately twofold higher in cultured L/L CCD than in +/+ CCD. Aldosterone (5 x 10(-7)M for 3 h) further increased I(eq) from cultured L/L CCD. Thus, this study brings three independent lines of evidence for the constitutive hyperactivity of ENaC in CCD from mice harboring the Liddle mutation.
Keywords
Aldosterone/urine Animals Body Weight Culture Techniques Disease Models, Animal Electrolytes/urine Epithelium/metabolism Kidney Tubules, Collecting/*metabolism Mice Mice, Transgenic Pseudohypoaldosteronism/*metabolism RNA, Messenger/metabolism Sodium Channels/*metabolism Syndrome
Pubmed
Web of science
Create date
24/01/2008 13:00
Last modification date
20/08/2019 14:59
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