ArticleThe Journal of membrane biology2005
Slow sodium channel inactivation and use-dependent block modulated by the same domain IV S6 residue.
Article in The Journal of membrane biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- A structural atlas of druggable sites on NaChannels (Austin, Tex.) · 2024Review
- Variant-specific therapy for long QT syndrome type 3.Heart rhythm · 2023Article
- Local Anesthetic Like Inhibition of the Cardiac NaJournal of experimental pharmacology · 2022Article
- Cation-π Interactions and their Functional Roles in Membrane Proteins.Journal of molecular biology · 2021Review
- Intersegment Contacts of Potentially Damaging Variants of Cardiac Sodium Channel.Frontiers in pharmacology · 2021Article
- Fibroblast growth factor homologous factors tune arrhythmogenic late NaV1.5 current in calmodulin binding-deficient channels.JCI insight · 2020Article
- Comparison of permeation mechanisms in sodium-selective ion channels.Neuroscience letters · 2019Review
- Modeling the human NaDrug design, development and therapy · 2017Article
- Understanding Sodium Channel Function and Modulation Using Atomistic Simulations of Bacterial Channel Structures.Current topics in membranes · 2016Article
- Aberrant sodium influx causes cardiomyopathy and atrial fibrillation in mice.The Journal of clinical investigation · 2016Article
- Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Ion conduction and conformational flexibility of a bacterial voltage-gated sodium channel.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Molecular basis for class Ib anti-arrhythmic inhibition of cardiac sodium channels.Nature communications · 2011Article
- Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies.Nature communications · 2011Article
- Structural determinants of drugs acting on the Nav1.8 channel.The Journal of biological chemistry · 2009Article
- Membrane permeable local anesthetics modulate Na(V)1.5 mechanosensitivity.Channels (Austin, Tex.)Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Voltage- and/or conformation-dependent association and dissociation of local anesthetic-class drugs from a putative receptor site in domain IV S6 of the sodium channel and slow conformation transitions of the drug-associated channel have been proposed as mechanisms of use- and frequency-dependent reduction in sodium current. To distinguish these possibilities, we have explored the reactivity to covalent modification by thiols and block of the mutations F1760C and F1760A at the putative receptor site of the cardiac sodium channel expressed as stable cell lines in HEK-293 cells. Both mutations decreased steady-state fast inactivation, shifting V1/2h from -86 +/- 1.3 mV (WT) to -72.3 +/- 1.4 mV (F1760C) and -67.7 +/- 1 mV (F1760A). In the absence of drug, the F1760C mutant channel displayed use-dependent current reduction during pulse-train stimulation, and faster onset of slow inactivation. This mutant also retained some sensitivity to lidocaine. In contrast, the F1760A mutant showed no use-dependent current reduction or sensitivity to lidocaine. The covalent-modifying agent MTS-ET enhanced use-dependent current reduction of the F1760C mutant channel only. The use-dependent reduction in current of the covalently modified channel completely recovered with rest. Lidocaine produced no additional block during exposure to MTS-ET-treated cells (MTS-ET 43 +/- 2.7%: MTS-ET lidocaine 47 +/- 4.5%), implying interaction at a common binding site. The data suggest that use-dependent binding at the F1760 site results in enhanced slow inactivation rather than alteration of drug association and dissociation from that site and may be a general mechanism of action of sodium-channel blocking agents.
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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.