ArticleThe Journal of general physiology1999
On the molecular basis of ion permeation in the epithelial Na+ channel.
Article in The Journal of general physiology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Ion Selectivity in the ENaC/DEG Family: A Systematic Review with Supporting Analysis.International journal of molecular sciences · 2021Pooled it
- Acid-sensing ion channel 2a assembles with epithelial NaThe Journal of biological chemistry · 2026Article
- Case Report: Functional investigation of the γENaC G532S mutation presenting as mild PHA-1B3.Frontiers in medicine · 2025Article
- Influence of proteolytic cleavage of ENaC's γ subunit upon NaAmerican journal of physiology. Renal physiology · 2024Article
- Epithelial NaComprehensive Physiology · 2024Review
- Absence of E-Cadherin and β-Catenin in the Basal Plasma Membrane of Collecting Duct Cells During NDI Development and Recovery.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2023Article
- The diverse functions of the DEG/ENaC family: linking genetic and physiological insights.The Journal of physiology · 2023Article
- Physiological insight into the conserved properties of Caenorhabditis elegans acid-sensing degenerin/epithelial sodium channels.The Journal of physiology · 2023Article
- A flexible GAS belt responds to pore mutations changing the ion selectivity of proton-gated channels.The Journal of general physiology · 2022Article
- The M1 and pre-M1 segments contribute differently to ion selectivity in ASICs and ENaCs.The Journal of general physiology · 2021Article
- Article
- Evolutionarily Conserved Interactions within the Pore Domain of Acid-Sensing Ion Channels.Biophysical journal · 2020Article
- Annexin II Light Chain p11 Interacts With ENaC to Increase Functional Activity at the Membrane.Frontiers in physiology · 2019Article
- Determinants of selective ion permeation in the epithelial NaThe Journal of general physiology · 2018Article
- Gating mechanisms of acid-sensing ion channels.Nature · 2018Article
- Epithelial transport inThe Journal of general physiology · 2017Review
- Modulation of the FMRFamide-gated NaPflugers Archiv : European journal of physiology · 2017Article
- Article
- Restoration of Epithelial Sodium Channel Function by Synthetic Peptides in Pseudohypoaldosteronism Type 1B Mutants.Frontiers in pharmacology · 2017Article
- Activation of the Human Epithelial Sodium Channel (ENaC) by Bile Acids Involves the Degenerin Site.The Journal of biological chemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epithelial Na+ channel (ENaC) is highly selective for Na+ and Li+ over K+ and is blocked by the diuretic amiloride. ENaC is a heterotetramer made of two alpha, one beta, and one gamma homologous subunits, each subunit comprising two transmembrane segments. Amino acid residues involved in binding of the pore blocker amiloride are located in the pre-M2 segment of beta and gamma subunits, which precedes the second putative transmembrane alpha helix (M2). A residue in the alpha subunit (alphaS589) at the NH2 terminus of M2 is critical for the molecular sieving properties of ENaC. ENaC is more permeable to Li+ than Na+ ions. The concentration of half-maximal unitary conductance is 38 mM for Na+ and 118 mM for Li+, a kinetic property that can account for the differences in Li+ and Na+ permeability. We show here that mutation of amino acid residues at homologous positions in the pre-M2 segment of alpha, beta, and gamma subunits (alphaG587, betaG529, gammaS541) decreases the Li+/Na+ selectivity by changing the apparent channel affinity for Li+ and Na+. Fitting single-channel data of the Li+ permeation to a discrete-state model including three barriers and two binding sites revealed that these mutations increased the energy needed for the translocation of Li+ from an outer ion binding site through the selectivity filter. Mutation of betaG529 to Ser, Cys, or Asp made ENaC partially permeable to K+ and larger ions, similar to the previously reported alphaS589 mutations. We conclude that the residues alphaG587 to alphaS589 and homologous residues in the beta and gamma subunits form the selectivity filter, which tightly accommodates Na+ and Li+ ions and excludes larger ions like K+.
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