Document Detail

Epithelial Na+ channel mutants causing Liddle's syndrome retain ability to respond to aldosterone and vasopressin.
MedLine Citation:
PMID:  12759227     Owner:  NLM     Status:  MEDLINE    
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.
Muriel Auberson; Nicole Hoffmann-Pochon; A Vandewalle; Stephan Kellenberger; Laurent Schild
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-05-20
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  285     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-07-31     Completed Date:  2003-09-12     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F459-71     Citation Subset:  IM    
Institut de Pharmacologie et Toxicologie, Université de Lausanne, Switzerland.
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MeSH Terms
Aldosterone / pharmacology*
Amiloride / analogs & derivatives*,  pharmacology
Cell Line
Electric Conductivity
Epithelial Cells / cytology,  drug effects*,  metabolism
Gene Expression
Hypertension / genetics*,  metabolism*
Mutation / genetics
Sodium Channels / genetics*,  metabolism*
Vasopressins / pharmacology*
Reg. No./Substance:
0/Sodium Channels; 11000-17-2/Vasopressins; 2609-46-3/Amiloride; 2898-76-2/benzamil; 52-39-1/Aldosterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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