Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Channels (Austin)
2014 Jan 01;85:444-51. doi: 10.4161/19336950.2014.949190.
Show Gene links
Show Anatomy links
Feedback inhibition of ENaC: acute and chronic mechanisms.
Patel AB
,
Yang L
,
Deng S
,
Palmer LG
.
???displayArticle.abstract???
Intracellular [Na(+)] ([Na(+)]i) modulates the activity of the epithelial Na channel (ENaC) to help prevent cell swelling and regulate epithelial Na(+) transport, but the underlying mechanisms remain unclear. We show here that short-term (60-80 min) incubation of ENaC-expressing oocytes in high Na(+) results in a 75% decrease in channel activity. When the β subunit was truncated, corresponding to a gain-of-function mutation found in Liddle's syndrome, the same maneuver reduced activity by 45% despite a larger increase in [Na(+)]i. In both cases the inhibition occurred with little to no change in cell-surface expression of γENaC. Long-term incubation (18 hours) in high Na(+) reduced activity by 92% and 75% in wild-type channels and Liddle's mutant, respectively, with concomitant 70% and 52% decreases in cell-surface γENaC. In the presence of Brefeldin A to inhibit forward protein trafficking, high-Na(+) incubation decreased wt ENaC activity by 52% and 88% after 4 and 8 hour incubations, respectively. Cleaved γENaC at the cell surface had lifetimes at the surface of 6 hrs in low Na(+) and 4 hrs in high Na(+), suggesting that [Na(+)]i increased the rate of retrieval of cleaved γ ENaC by 50%. This implies that enhanced retrieval of ENaC channels at the cell surface accounts for part, but not all, of the downregulation of ENaC activity shown with chronic increases in [Na(+)]i.
Abriel,
Feedback inhibition of rat amiloride-sensitive epithelial sodium channels expressed in Xenopus laevis oocytes.
1999, Pubmed,
Xenbase
Abriel,
Feedback inhibition of rat amiloride-sensitive epithelial sodium channels expressed in Xenopus laevis oocytes.
1999,
Pubmed
,
Xenbase
Abriel,
Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle's syndrome.
1999,
Pubmed
,
Xenbase
Anantharam,
Open probability of the epithelial sodium channel is regulated by intracellular sodium.
2006,
Pubmed
,
Xenbase
Awayda,
Regulation of the epithelial Na(+) channel by intracellular Na(+).
1999,
Pubmed
,
Xenbase
Bruns,
Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit.
2007,
Pubmed
,
Xenbase
Canessa,
Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits.
1994,
Pubmed
,
Xenbase
Chase,
Regulation of the sodium permeability of the luminal border of toad bladder by intracellular sodium and calcium: role of sodium-calcium exchange in the basolateral membrane.
1981,
Pubmed
Dinudom,
Control of the amiloride-sensitive Na+ current in mouse salivary ducts by intracellular anions is mediated by a G protein.
1995,
Pubmed
Dinudom,
Nedd4 mediates control of an epithelial Na+ channel in salivary duct cells by cytosolic Na+.
1998,
Pubmed
Ergonul,
Regulation of maturation and processing of ENaC subunits in the rat kidney.
2006,
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
Harvey,
All three WW domains of murine Nedd4 are involved in the regulation of epithelial sodium channels by intracellular Na+.
1999,
Pubmed
Kellenberger,
Mutations causing Liddle syndrome reduce sodium-dependent downregulation of the epithelial sodium channel in the Xenopus oocyte expression system.
1998,
Pubmed
,
Xenbase
Kirk,
Passive cation permeability of turtle colon: evidence for a negative interaction between intracellular sodium and apical sodium permeability.
1985,
Pubmed
Knight,
Intracellular sodium regulates proteolytic activation of the epithelial sodium channel.
2008,
Pubmed
Komwatana,
Cytosolic Na+ controls and epithelial Na+ channel via the Go guanine nucleotide-binding regulatory protein.
1996,
Pubmed
Konstas,
Regulation of the epithelial sodium channel by N4WBP5A, a novel Nedd4/Nedd4-2-interacting protein.
2002,
Pubmed
,
Xenbase
Ling,
Effects of luminal Na+ on single Na+ channels in A6 cells, a regulatory role for protein kinase C.
1989,
Pubmed
MACROBBIE,
Osmotic behaviour of the epithelial cells of frog skin.
1961,
Pubmed
Malik,
Role of Nedd4-2 and polyubiquitination in epithelial sodium channel degradation in untransfected renal A6 cells expressing endogenous ENaC subunits.
2005,
Pubmed
,
Xenbase
Patel,
Tissue kallikrein activation of the epithelial Na channel.
2012,
Pubmed
,
Xenbase
Rotin,
Ubiquitination and endocytosis of plasma membrane proteins: role of Nedd4/Rsp5p family of ubiquitin-protein ligases.
2000,
Pubmed
Ruffieux-Daidié,
Deubiquitylation regulates activation and proteolytic cleavage of ENaC.
2008,
Pubmed
Ruffieux-Daidié,
Intracellular ubiquitylation of the epithelial Na+ channel controls extracellular proteolytic channel activation via conformational change.
2011,
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
Shimkets,
The activity of the epithelial sodium channel is regulated by clathrin-mediated endocytosis.
1997,
Pubmed
,
Xenbase
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
Turnheim,
Interaction between cell sodium and the amiloride-sensitive sodium entry step in rabbit colon.
1978,
Pubmed
Van Driessche,
Noise analysis of inward and outward Na+ currents across the apical border of ouabain-treated frog skin.
1983,
Pubmed
Volk,
Extracellular Na+ removal attenuates rundown of the epithelial Na+-channel (ENaC) by reducing the rate of channel retrieval.
2004,
Pubmed
,
Xenbase
Wiemuth,
Epithelial sodium channel (ENaC) is multi-ubiquitinated at the cell surface.
2007,
Pubmed
Zhou,
Nedd4-2 catalyzes ubiquitination and degradation of cell surface ENaC.
2007,
Pubmed
