ArticleProceedings of the National Academy of Sciences of the United States of America1994
A mutation in segment IVS6 disrupts fast inactivation of sodium channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
58 citing papers in PubMed, 123 citations in OpenAlex.
- The crucial decade that ion channels were proven to exist : The vision of Bertil Hille and Clay Armstrong and how it came through.Pflugers Archiv : European journal of physiology · 2025Review
- Conformational photo-trapping in NaBiophysical journal · 2024Article
- Cannabidiol inhibits NaNature communications · 2023Article
- Structural Advances in Voltage-Gated Sodium Channels.Frontiers in pharmacology · 2022Review
- Sodium channelopathies of skeletal muscle and brain.Physiological reviews · 2021Review
- Article
- NaBiophysical journal · 2021Review
- A Novel Spider Toxin Inhibits Fast Inactivation of the NaFrontiers in pharmacology · 2021Article
- Structure of the Cardiac Sodium Channel.Cell · 2020Article
- Effects of FGF14 and NaThe Journal of general physiology · 2019Article
- Structural basis for antiarrhythmic drug interactions with the human cardiac sodium channel.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Article
- Distinct modulation of inactivation by a residue in the pore domain of voltage-gated NaScientific reports · 2018Article
- Mechanisms and models of cardiac sodium channel inactivation.Channels (Austin, Tex.) · 2017Review
- Annotation of functional impact of voltage-gated sodium channel mutations.Human mutation · 2017Article
- Small molecule modulation of voltage gated sodium channels.Current opinion in structural biology · 2017Review
- Regulation of NaThe Journal of general physiology · 2017Article
- Single amino acid deletion in transmembrane segment D4S6 of sodium channel Scn8a (Nav1.6) in a mouse mutant with a chronic movement disorder.Neurobiology of disease · 2016Article
- The hitchhiker's guide to the voltage-gated sodium channel galaxy.The Journal of general physiology · 2016Review
- Exploring the structure of the voltage-gated Na+ channel by an engineered drug access pathway to the receptor site for local anesthetics.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Na(+)-channel inactivation is proposed to occur by binding of an intracellular inactivation gate to a hydrophobic inactivation gate receptor in the intracellular mouth of the pore. Amino acid residues in transmembrane segment S6 of domain IV (IVS6) that are critical for fast inactivation were identified by alanine-scanning mutagenesis. Mutant VIL1774-6AAA, in which three adjacent residues (Val-Ile-Leu) at the intracellular end of segment IVS6 were converted to alanine, had substantial (> 85%) sustained Na+ currents remaining 15 ms after depolarization, while a nearby mutation of three residues to alanine had no effect. Single-channel analysis revealed continued reopenings late in 40-ms depolarizing pulses indicating that inactivation was substantially impaired compared to wild type. The mean open time for VIL1774-6AAA was longer than wild type, suggesting that this mutation also decreases the rate of entry into the fast inactivated state. These results suggest that residues near the intracellular end of segment IVS6 are critical for fast Na(+)-channel inactivation and may form part of the hydrophobic receptor site for the fast inactivation gate.
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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.