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.
???displayArticle.abstract???
Epithelial Na(+) channel (ENaC) subunits (α, β, and γ) found in functional complexes are translated from mature mRNAs that are similarly processed by the inclusion of 13 canonical exons. We examined whether individual exons 3-12, encoding the large extracellular domain, are required for functional channel expression. Human ENaCs with an in-frame deletion of a single α-subunit exon were expressed in Xenopus oocytes, and their functional properties were examined by two-electrode voltage clamp. With the exception of exon 11, deletion of an individual exon eliminated channel activity. Channels lacking α-subunit exon 11 were hyperactive. Oocytes expressing this mutant exhibited fourfold greater amiloride-sensitive whole cell currents than cells expressing wild-type channels. A parallel fivefold increase in channel open probability was observed with channels lacking α-subunit exon 11. These mutant channels also exhibited a lost of Na(+) self-inhibition, whereas we found similar levels of surface expression of mutant and wild-type channels. In contrast, in-frame deletions of exon 11 from either the β- or γ-subunit led to a significant loss of channel activity, in association with a marked decrease in surface expression. Our results suggest that exon 11 within the three human ENaC genes encodes structurally homologous yet functionally diverse domains and that exon 11 in the α-subunit encodes a module that regulates channel gating.
Abecasis,
An integrated map of genetic variation from 1,092 human genomes.
2012, Pubmed
Abecasis,
An integrated map of genetic variation from 1,092 human genomes.
2012,
Pubmed Adachi,
Compound heterozygous mutations in the gamma subunit gene of ENaC (1627delG and 1570-1G-->A) in one sporadic Japanese patient with a systemic form of pseudohypoaldosteronism type 1.
2001,
Pubmed Baconguis,
Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.
2012,
Pubmed Baines,
Kinases as targets for ENaC regulation.
2013,
Pubmed Baker,
Amiloride, a specific drug for hypertension in black people with T594M variant?
2002,
Pubmed Banasikowska,
Expression of epithelial sodium channel alpha-subunit mRNAs with alternative 5'-untranslated regions in the developing human lung.
2004,
Pubmed Bruns,
Epithelial Na+ channels are fully activated by furin- and prostasin-dependent release of an inhibitory peptide from the gamma-subunit.
2007,
Pubmed
,
Xenbase Bubien,
Epithelial Na+ channel (ENaC), hormones, and hypertension.
2010,
Pubmed Buck,
The endoplasmic reticulum-associated degradation of the epithelial sodium channel requires a unique complement of molecular chaperones.
2010,
Pubmed
,
Xenbase Buck,
The Lhs1/GRP170 chaperones facilitate the endoplasmic reticulum-associated degradation of the epithelial sodium channel.
2013,
Pubmed
,
Xenbase Büsst,
The epithelial sodium channel γ-subunit gene and blood pressure: family based association, renal gene expression, and physiological analyses.
2011,
Pubmed Büsst,
Blood pressure regulation via the epithelial sodium channel: from gene to kidney and beyond.
2013,
Pubmed Carattino,
Arachidonic acid regulates surface expression of epithelial sodium channels.
2003,
Pubmed
,
Xenbase Chen,
Probing the structural basis of Zn2+ regulation of the epithelial Na+ channel.
2012,
Pubmed
,
Xenbase Chen,
Gain-of-function variant of the human epithelial sodium channel.
2013,
Pubmed
,
Xenbase Chen,
External Cu2+ inhibits human epithelial Na+ channels by binding at a subunit interface of extracellular domains.
2011,
Pubmed
,
Xenbase Chow,
Hormonal regulation and genomic organization of the human amiloride-sensitive epithelial sodium channel alpha subunit gene.
1999,
Pubmed Collier,
Identification of epithelial Na+ channel (ENaC) intersubunit Cl- inhibitory residues suggests a trimeric alpha gamma beta channel architecture.
2011,
Pubmed
,
Xenbase Collier,
Extracellular protons regulate human ENaC by modulating Na+ self-inhibition.
2009,
Pubmed
,
Xenbase Djebali,
Landscape of transcription in human cells.
2012,
Pubmed Firsov,
Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: a quantitative approach.
1996,
Pubmed
,
Xenbase Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed Hannila-Handelberg,
Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension.
2005,
Pubmed
,
Xenbase Hughey,
Distinct pools of epithelial sodium channels are expressed at the plasma membrane.
2004,
Pubmed
,
Xenbase Hughey,
Epithelial sodium channels are activated by furin-dependent proteolysis.
2004,
Pubmed
,
Xenbase Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed Jones,
The R563Q mutation of the epithelial sodium channel beta-subunit is associated with hypertension.
2011,
Pubmed Jones,
The association of the R563Q genotype of the ENaC with phenotypic variation in Southern Africa.
2012,
Pubmed Kashlan,
ENaC structure and function in the wake of a resolved structure of a family member.
2011,
Pubmed Kashlan,
Constraint-based, homology model of the extracellular domain of the epithelial Na+ channel α subunit reveals a mechanism of channel activation by proteases.
2011,
Pubmed Kashlan,
Epithelial Na(+) channel regulation by cytoplasmic and extracellular factors.
2012,
Pubmed Kellenberger,
Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure.
2002,
Pubmed Li,
Asymmetric organization of the pore region of the epithelial sodium channel.
2003,
Pubmed
,
Xenbase Mall,
Role of the amiloride-sensitive epithelial Na+ channel in the pathogenesis and as a therapeutic target for cystic fibrosis lung disease.
2009,
Pubmed Mueller,
Cys palmitoylation of the beta subunit modulates gating of the epithelial sodium channel.
2010,
Pubmed
,
Xenbase Mueller,
Epithelial sodium channel exit from the endoplasmic reticulum is regulated by a signal within the carboxyl cytoplasmic domain of the alpha subunit.
2007,
Pubmed Oh,
An Alu cassette in the human epithelial sodium channel.
2001,
Pubmed
,
Xenbase Pratt,
Central role for ENaC in development of hypertension.
2005,
Pubmed Rossier,
Epithelial sodium channel and the control of sodium balance: interaction between genetic and environmental factors.
2002,
Pubmed 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 Sheng,
Functional role of extracellular loop cysteine residues of the epithelial Na+ channel in Na+ self-inhibition.
2007,
Pubmed
,
Xenbase Sheng,
Extracellular Zn2+ activates epithelial Na+ channels by eliminating Na+ self-inhibition.
2004,
Pubmed
,
Xenbase Sheng,
External nickel inhibits epithelial sodium channel by binding to histidine residues within the extracellular domains of alpha and gamma subunits and reducing channel open probability.
2002,
Pubmed
,
Xenbase Sheng,
Extracellular histidine residues crucial for Na+ self-inhibition of epithelial Na+ channels.
2004,
Pubmed
,
Xenbase Shi,
Base of the thumb domain modulates epithelial sodium channel gating.
2011,
Pubmed
,
Xenbase Shi,
ENaC regulation by proteases and shear stress.
2013,
Pubmed Shi,
Gamma subunit second transmembrane domain contributes to epithelial sodium channel gating and amiloride block.
2013,
Pubmed
,
Xenbase Shi,
Extracellular finger domain modulates the response of the epithelial sodium channel to shear stress.
2012,
Pubmed
,
Xenbase Soundararajan,
Role of epithelial sodium channels and their regulators in hypertension.
2010,
Pubmed Stockand,
Insight toward epithelial Na+ channel mechanism revealed by the acid-sensing ion channel 1 structure.
2008,
Pubmed Strautnieks,
A novel splice-site mutation in the gamma subunit of the epithelial sodium channel gene in three pseudohypoaldosteronism type 1 families.
1996,
Pubmed Thomas,
5' heterogeneity in epithelial sodium channel alpha-subunit mRNA leads to distinct NH2-terminal variant proteins.
1998,
Pubmed
,
Xenbase Tucker,
Cloning and functional studies of splice variants of the alpha-subunit of the amiloride-sensitive Na+ channel.
1998,
Pubmed
,
Xenbase Welzel,
Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1.
2013,
Pubmed Winarski,
Extracellular allosteric regulatory subdomain within the gamma subunit of the epithelial Na+ channel.
2010,
Pubmed
,
Xenbase Zhao,
Common variants in epithelial sodium channel genes contribute to salt sensitivity of blood pressure: The GenSalt study.
2011,
Pubmed
