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Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system.
Kellenberger S
,
Gautschi I
,
Rossier BC
,
Schild L
.
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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 distalnephron that has important implications for the pathogenesis of hypertension.
Beck,
Inhibition of angiotensin-converting enzyme modulates structural and functional adaptation to loop diuretic-induced diuresis.
1997, Pubmed
Beck,
Inhibition of angiotensin-converting enzyme modulates structural and functional adaptation to loop diuretic-induced diuresis.
1997,
Pubmed
Blazer-Yost,
The amiloride-sensitive epithelial Na+ channel: binding sites and channel densities.
1997,
Pubmed
Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase
Chen,
The WW domain of Yes-associated protein binds a proline-rich ligand that differs from the consensus established for Src homology 3-binding modules.
1995,
Pubmed
Favre,
On the structural basis for ionic selectivity among Na+, K+, and Ca2+ in the voltage-gated sodium channel.
1996,
Pubmed
,
Xenbase
Firsov,
Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach.
1996,
Pubmed
,
Xenbase
Flemmer,
Transcellular sodium transport and basolateral rubidium uptake in the isolated perfused cortical collecting duct.
1993,
Pubmed
Frindt,
Feedback regulation of Na channels in rat CCT. III. Response to cAMP.
1995,
Pubmed
Frindt,
Feedback regulation of Na channels in rat CCT. IV. Mediation by activation of protein kinase C.
1996,
Pubmed
Frindt,
Feedback regulation of Na channels in rat CCT. II. Effects of inhibition of Na entry.
1993,
Pubmed
Garty,
Epithelial sodium channels: function, structure, and regulation.
1997,
Pubmed
Hansson,
A de novo missense mutation of the beta subunit of the epithelial sodium channel causes hypertension and Liddle syndrome, identifying a proline-rich segment critical for regulation of channel activity.
1995,
Pubmed
,
Xenbase
Hansson,
Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome.
1995,
Pubmed
,
Xenbase
Hummler,
Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice.
1996,
Pubmed
,
Xenbase
Komwatana,
Cytosolic Na+ controls and epithelial Na+ channel via the Go guanine nucleotide-binding regulatory protein.
1996,
Pubmed
MACROBBIE,
Osmotic behaviour of the epithelial cells of frog skin.
1961,
Pubmed
Palmer,
Gating of Na channels in the rat cortical collecting tubule: effects of voltage and membrane stretch.
1996,
Pubmed
Rossier,
Epithelial sodium channels.
1994,
Pubmed
Schild,
A mutation in the epithelial sodium channel causing Liddle disease increases channel activity in the Xenopus laevis oocyte expression system.
1995,
Pubmed
,
Xenbase
Schild,
Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome.
1996,
Pubmed
,
Xenbase
Schild,
Identification of amino acid residues in the alpha, beta, and gamma subunits of the epithelial sodium channel (ENaC) involved in amiloride block and ion permeation.
1997,
Pubmed
,
Xenbase
Schlatter,
Correlation between intracellular activities of Ca2+ and Na+ in rat cortical collecting duct--A possible coupling mechanism between Na+-K+-ATPase and Basolateral K+ conductance.
1996,
Pubmed
Shimkets,
The activity of the epithelial sodium channel is regulated by clathrin-mediated endocytosis.
1997,
Pubmed
,
Xenbase
Shimkets,
Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel.
1994,
Pubmed
Silver,
Feedback regulation of Na channels in rat CCT. I. Effects of inhibition of Na pump.
1993,
Pubmed
Snyder,
Mechanism by which Liddle's syndrome mutations increase activity of a human epithelial Na+ channel.
1995,
Pubmed
,
Xenbase
Staub,
WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome.
1996,
Pubmed
Staub,
Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination.
1997,
Pubmed
,
Xenbase
Stoos,
Nitric oxide inhibits sodium reabsorption in the isolated perfused cortical collecting duct.
1995,
Pubmed
Tamura,
Liddle disease caused by a missense mutation of beta subunit of the epithelial sodium channel gene.
1996,
Pubmed
,
Xenbase
