ArticleProceedings of the National Academy of Sciences of the United States of America1996
Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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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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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- An Updated Meta-Analysis Based on the Preclinical Evidence of Mechanism of Aconitine-Induced Cardiotoxicity.Frontiers in pharmacology · 2022Pooled it
- Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review.Clinical cardiology · 2009Pooled it
- Beneficial action potential duration-shortening effects, but deleterious negative inotropism of IKs-activator docosahexaenoyl glycine in long QT syndrome type 2.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- The differential impacts of equivalent gating-charge mutations in voltage-gated sodium channels.The Journal of general physiology · 2025Article
- ELUCIDATING THE DIFFERENTIAL IMPACTS OF EQUIVALENT GATING-CHARGE MUTATIONS IN VOLTAGE-GATED SODIUM CHANNELS.bioRxiv : the preprint server for biology · 2024Article
- Activation of hTREK-1 by polyunsaturated fatty acids involves direct interaction.Scientific reports · 2024Article
- Assessing the impact of omega-3 fatty acids on ventricular tachyarrhythmia and survival in patients with ICDs: A systematic review and meta-analysis.International journal of cardiology. Heart & vasculature · 2024Review
- Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids.International journal of molecular sciences · 2023Review
- Perspectives on Potential Fatty Acid Modulations of Motility Associated Human Sperm Ion Channels.International journal of molecular sciences · 2022Review
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Review
- Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers.iScience · 2021Review
- Maternal Fatty Acid Metabolism in Pregnancy and Its Consequences in the Feto-Placental Development.Frontiers in physiology · 2021Review
- Polyunsaturated fatty acid-derived IActa physiologica (Oxford, England) · 2020Article
- Article
- ω-6 and ω-9 polyunsaturated fatty acids with double bonds near the carboxyl head have the highest affinity and largest effects on the cardiac IActa physiologica (Oxford, England) · 2019Article
- FABP3 in the Anterior Cingulate Cortex Modulates the Methylation Status of the Glutamic Acid DecarboxylaseThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Inhibitors of connexin and pannexin channels as potential therapeutics.Pharmacology & therapeutics · 2017Review
- Cardioprotective effects of omega 3 fatty acids: origin of the variability.Journal of muscle research and cell motility · 2017Review
- Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels.Frontiers in physiology · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The effects of free polyunsaturated fatty acids (PUFA) on the binding of ligands to receptors on voltage-sensitive Na+ channels of neonatal rat cardiac myocytes were assessed. The radioligand was [benzoyl-2,5-(3)H] batrachotoxinin A 20alpha-benzoate ([(3)H]BTXB), a toxin that binds to the Na+ channel. The PUFA that have been shown to be antiarrhythmic, including eicosapentaenoic acid (EPA; C20:5n-3), docosahexaenoic acid (DHA; C22:6n-3), eicosatetraynoic acid (ETYA), linolenic acid (C18:3n-3), and linoleic acid (C18:2n-6), inhibited [(3)H]BTXB binding in a dose-dependent fashion with IC50 values of 28-35 microM, whereas those fatty acids that have no antiarrhythmic effects including saturated fatty acid (stearic acid, C18:0), monounsaturated fatty acid (oleic acid; C18:1n-9), and EPA methyl ester did not have a significant effect on [(3)H]BTXB binding. Enrichment of the myocyte membrane with cholesterol neither affected [(3)H]BTXB binding when compared with control cells nor altered the inhibitory effects of PUFA on [(3)H]BTXB binding. Scatchard analysis of [(3)H]BTXB binding showed that EPA reduced the maximal binding without altering the Kd for [(3)H]BTXB binding, indicating allosteric inhibition. The inhibition by EPA of [(3)H]BTXB binding was reversible (within 30 min) when delipidated bovine serum albumin was added. The binding of the PUFA to this site on the Na+ channel is reversible and structure-specific and occurs at concentrations close to those required for apparent antiarrhythmic effects and a blocking effect on the Na+ current, suggesting that binding of the PUFA at this site relates to their antiarrhythmic action.
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Registered trials
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