Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin.

Détails

ID Serval
serval:BIB_457CA96E5626
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin.
Périodique
American Journal of Physiology. Renal Physiology
Auteur(s)
Auberson M., Hoffmann-Pochon N., Vandewalle A., Kellenberger S., Schild L.
ISSN
0363-6127[print], 0363-6127[linking]
Statut éditorial
Publié
Date de publication
2003
Volume
285
Numéro
3
Pages
F459-F471
Langue
anglais
Résumé
Liddle's syndrome is a monogenic form of hypertension caused by mutations in the PY motif of the COOH terminus of beta- and gamma-epithelial Na+ channel (ENaC) subunits. These mutations lead to retention of active channels at the cell surface. Because of the critical role of this PY motif in the stability of ENaCs at the cell surface, we have investigated its contribution to the ENaC response to aldosterone and vasopressin. Mutants of the PY motif in beta- and gamma-ENaC subunits (beta-Y618A, beta-P616L, beta-R564stop, and gamma-K570stop) were stably expressed by retroviral gene transfer in a renal cortical collecting duct cell line (mpkCCDcl4), and transepithelial Na+ transport was assessed by measurements of the benzamil-sensitive short-circuit current (Isc). Cells that express ENaC mutants of the PY motif showed a five- to sixfold higher basal Isc compared with control cells and responded to stimulation by aldosterone (10(-6) M) or vasopressin (10(-9) M) with a further increase in Isc. The rates of the initial increases in Isc after aldosterone or vasopressin stimulation were comparable in cells transduced with wild-type and mutant ENaCs, but reversal of the effects of aldosterone and vasopressin was slower in cells that expressed the ENaC mutants. The conserved sensitivity of ENaC mutants to stimulation by aldosterone and vasopressin together with the prolonged activity at the cell surface likely contribute to the increased Na+ absorption in the distal nephron of patients with Liddle's syndrome.
Mots-clé
Aldosterone/pharmacology, Amiloride/analogs & derivatives, Amiloride/pharmacology, Animals, Cell Line, Electric Conductivity, Epithelial Cells/cytology, Epithelial Cells/drug effects, Gene Expression, Humans, Hypertension/genetics, Hypertension/metabolism, Mice, Mutation/genetics, Sodium Channels/genetics, Sodium Channels/metabolism, Syndrome, Vasopressins/pharmacology
Pubmed
Web of science
Création de la notice
24/01/2008 13:45
Dernière modification de la notice
03/03/2018 16:45
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