Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system.

Détails

ID Serval
serval:BIB_A8764EEF929C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system.
Périodique
Journal of Clinical Investigation
Auteur(s)
Kellenberger S., Gautschi I., Rossier B.C., Schild L.
ISSN
0021-9738[print], 0021-9738[linking]
Statut éditorial
Publié
Date de publication
1998
Volume
101
Numéro
12
Pages
2741-2750
Langue
anglais
Résumé
Liddle syndrome is an autosomal dominant form of hypertension resulting from deletion or missense mutations of a PPPxY motif in the cytoplasmic COOH terminus of either the beta or gamma subunit of the epithelial Na channel (ENaC). These mutations lead to increased channel activity. In this study we show that wild-type ENaC is downregulated by intracellular Na+, and that Liddle mutants decrease the channel sensitivity to inhibition by intracellular Na+. This event results at high intracellular Na+ activity in 1.2-2.4-fold higher cell surface expression, and 2.8-3.5-fold higher average current per channel in Liddle mutants compared with the wild type. In addition, we show that a rapid increase in the intracellular Na+ activity induced downregulation of the activity of wild-type ENaC, but not Liddle mutants, on a time scale of minutes, which was directly correlated to the magnitude of the Na+ influx into the oocytes. Feedback inhibition of ENaC by intracellular Na+ likely represents an important cellular mechanism for controlling Na+ reabsorption in the distal nephron that has important implications for the pathogenesis of hypertension.
Mots-clé
Animals, Down-Regulation, Epithelial Cells/physiology, Humans, Hypertension/genetics, Mutation, Rats, Sodium/physiology, Sodium Channels/genetics, Transfection, Xenopus
Pubmed
Web of science
Création de la notice
24/01/2008 13:45
Dernière modification de la notice
20/08/2019 16:12
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