ArticleThe Journal of biological chemistry2011
External Cu2+ inhibits human epithelial Na+ channels by binding at a subunit interface of extracellular domains.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- A novel dominant hyperekplexia mutation Y705C alters trafficking and biochemical properties of the presynaptic glycine transporter GlyT2.The Journal of biological chemistry · 2012Trial
- Copper (CuPharmaceuticals (Basel, Switzerland) · 2026Article
- Epithelial NaComprehensive Physiology · 2024Review
- Accessibility of ENaC extracellular domain central core residues.The Journal of biological chemistry · 2022Article
- Molecular principles of assembly, activation, and inhibition in epithelial sodium channel.eLife · 2020Article
- Analyses of epithelial NaThe Journal of biological chemistry · 2019Article
- New insights regarding epithelial Na+ channel regulation and its role in the kidney, immune system and vasculature.Current opinion in nephrology and hypertension · 2019Review
- Thumb domains of the three epithelial NaThe Journal of biological chemistry · 2018Article
- Article
- Conserved cysteines in the finger domain of the epithelial NaThe Journal of biological chemistry · 2018Article
- Specific Palmitoyltransferases Associate with and Activate the Epithelial Sodium Channel.The Journal of biological chemistry · 2017Article
- Functional Roles of Clusters of Hydrophobic and Polar Residues in the Epithelial Na+ Channel Knuckle Domain.The Journal of biological chemistry · 2015Article
- Na+ inhibits the epithelial Na+ channel by binding to a site in an extracellular acidic cleft.The Journal of biological chemistry · 2015Article
- Intersubunit conformational changes mediate epithelial sodium channel gating.The Journal of general physiology · 2014Article
- Deletion of α-subunit exon 11 of the epithelial Na+ channel reveals a regulatory module.American journal of physiology. Renal physiology · 2014Article
- SILAC-based quantitative proteomic analysis of human lung cell response to copper oxide nanoparticles.PloS one · 2014Article
- Article
- Probing the structural basis of Zn2+ regulation of the epithelial Na+ channel.The Journal of biological chemistry · 2012Article
- ENaC structure and function in the wake of a resolved structure of a family member.American journal of physiology. Renal physiology · 2011Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Epithelial Na(+) channels (ENaCs) play an essential role in the regulation of body fluid homeostasis. Certain transition metals activate or inhibit the activity of ENaCs. In this study, we examined the effect of extracellular Cu(2+) on human ENaC expressed in Xenopus oocytes and investigated the structural basis for its effects. External Cu(2+) inhibited human αβγ ENaC with an estimated IC(50) of 0.3 μM. The slow time course and a lack of change in the current-voltage relationship were consistent with an allosteric (non pore-plugging) inhibition of human ENaC by Cu(2+). Experiments with mixed human and mouse ENaC subunits suggested that both the α and β subunits were primarily responsible for the inhibitory effect of Cu(2+) on human ENaC. Lowering bath solution pH diminished the inhibition by Cu(2+). Mutations of two α, two β, and two γ His residues within extracellular domains significantly reduced the inhibition of human ENaC by Cu(2+). We identified a pair of residues as potential Cu(2+)-binding sites at the subunit interface between thumb subdomain of αhENaC and palm subdomain of βhENaC, suggesting a counterclockwise arrangement of α, β, and γ ENaC subunits in a trimeric channel complex when viewed from above. We conclude that extracellular Cu(2+) is a potent inhibitor of human ENaC and binds to multiple sites within the extracellular domains including a subunit interface.
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Registered trials
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