ArticleThe Journal of physiology2006
A conserved ring of charge in mammalian Na+ channels: a molecular regulator of the outer pore conformation during slow inactivation.
Article in The Journal of physiology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Preorganized Electric Fields in Voltage-Gated Sodium Channels.Chembiochem : a European journal of chemical biology · 2025Article
- Voltage gated sodium and calcium channels: Discovery, structure, function, and Pharmacology.Channels (Austin, Tex.) · 2023Review
- Article
- Large-effect mutations generate trade-off between predatory and locomotor ability during arms race coevolution with deadly prey.Evolution letters · 2018Article
- Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels II: a periodic paralysis mutation in Na(V)1.4 (L689I).The Journal of general physiology · 2013Article
- Voltage-sensor movements describe slow inactivation of voltage-gated sodium channels I: wild-type skeletal muscle Na(V)1.4.The Journal of general physiology · 2013Article
- Use-dependent block of the voltage-gated Na(+) channel by tetrodotoxin and saxitoxin: effect of pore mutations that change ionic selectivity.The Journal of general physiology · 2012Article
- Gating transitions in the selectivity filter region of a sodium channel are coupled to the domain IV voltage sensor.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Biophysical costs associated with tetrodotoxin resistance in the sodium channel pore of the garter snake, Thamnophis sirtalis.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2011Article
- A molecular switch between the outer and the inner vestibules of the voltage-gated Na+ channel.The Journal of biological chemistry · 2010Article
- The outer vestibule of the Na+ channel-toxin receptor and modulator of permeation as well as gating.Marine drugs · 2010Review
- Novel molecular determinants in the pore region of sodium channels regulate local anesthetic binding.Molecular pharmacology · 2009Article
- Correlations between clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in the cardiac Na+ channel.Acta physiologica (Oxford, England) · 2008Article
- Speeding the recovery from ultraslow inactivation of voltage-gated Na+ channels by metal ion binding to the selectivity filter: a foot-on-the-door?Biophysical journal · 2007Article
- Sodium channels: ionic model of slow inactivation and state-dependent drug binding.Biophysical journal · 2007Article
- Docking of mu-conotoxin GIIIA in the sodium channel outer vestibule.Channels (Austin, Tex.)Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The molecular mechanisms underlying slow inactivation in sodium channels are elusive. Our results suggest that EEDD, a highly conserved ring of charge in the external vestibule of mammalian voltage-gated sodium channels, undermines slow inactivation. By employing site-directed mutagenesis, we found that charge alterations in this asymmetric yet strong local electrostatic field of the EEDD ring significantly altered the kinetics of slow inactivation gating. Using a non-linear Poisson-Boltzmann equation, quantitative computations of the electrostatic field in a sodium channel structural model suggested a significant electrostatic repulsion between residues E403 and E758 at close proximity. Interestingly, when this electrostatic interaction was eliminated by the double mutation E403C + E758C, the kinetics of recovery from slow inactivation of the double-mutant channel was retarded by 2500% compared to control. These data suggest that the EEDD ring, located within the asymmetric electric field, is a molecular motif that critically modulates slow inactivation in sodium channels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.