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
ISSN
1046-6673 (Print)
ISSN-L
1046-6673
Publication state
Published
Issued date
09/2003
Peer-reviewed
Oui
Volume
14
Number
9
Pages
2219-2228
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Publication Status: ppublish
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
Open Access
Yes
Create date
24/01/2008 13:00
Last modification date
09/04/2024 6:13