ArticleHeart rhythm2013
Antiarrhythmic effects of the highly selective late sodium channel current blocker GS-458967.
Article in Heart rhythm, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 87 citations in OpenAlex.
- Conventional Antiarrhythmics Class I-IV, Late INa Inhibitors, IKs Enhancers, RyR2 Stabilizers, Gap Junction Modulators, Atrial-Selective Antiarrhythmics, and Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Therapy in Arrhythmias.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Effects of GS-967, GS-6615 and ranolazine on the responses of the rabbit aorta to adrenergic nerve stimulation.Frontiers in physiology · 2025Article
- Characterization of novel arrhythmogenic patterns arising secondary to heterogeneous expression and activation of Nav1.8.Frontiers in cardiovascular medicine · 2025Article
- Automaticity of the Pulmonary Vein Myocardium and the Effect of Class I Antiarrhythmic Drugs.International journal of molecular sciences · 2024Review
- Voltage-Gated Ion Channel Compensatory Effect in DEE: Implications for Future Therapies.Cells · 2024Review
- Late Sodium Current of the Heart: Where Do We Stand and Where Are We Going?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Ranolazine: An Old Drug with Emerging Potential; Lessons from Pre-Clinical and Clinical Investigations for Possible Repositioning.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Suppression of ventricular arrhythmias by targeting late L-type Ca2+ current.The Journal of general physiology · 2021Article
- Late sodium current and calcium homeostasis in arrhythmogenesis.Channels (Austin, Tex.) · 2021Review
- Calcium Signaling Silencing in Atrial Fibrillation: Implications for Atrial Sodium Homeostasis.International journal of molecular sciences · 2021Review
- Mexiletine-like cellular electrophysiological effects of GS967 in canine ventricular myocardium.Scientific reports · 2021Article
- Late ICirculation. Arrhythmia and electrophysiology · 2020Article
- The Citrus Flavonoid Hesperetin Has an Inadequate Anti-Arrhythmic Profile in the ΔKPQ NaBiomolecules · 2020Article
- Pulmonary Delivery of Antiarrhythmic Drugs for Rapid Conversion of New-Onset Atrial Fibrillation.Journal of cardiovascular pharmacology · 2020Review
- Late Sodium Current Inhibitors as Potential Antiarrhythmic Agents.Frontiers in pharmacology · 2020Review
- Prax330 reduces persistent and resurgent sodium channel currents and neuronal hyperexcitability of subiculum neurons in a mouse model of SCN8A epileptic encephalopathy.Neuropharmacology · 2019Article
- Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes.Journal of biomedical science · 2019Article
- The Association Between Diabetes Mellitus and Atrial Fibrillation: Clinical and Mechanistic Insights.Frontiers in physiology · 2019Review
- The transient receptor potential melastatin 4 channel inhibitor 9-phenanthrol modulates cardiac sodium channel.British journal of pharmacology · 2018Article
- Substrates and potential therapeutics of ventricular arrhythmias in heart failure.European journal of pharmacology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPrevious studies have shown that late sodium channel current (INa) blockers such as ranolazine can exert antiarrhythmic effects by suppressing early and delayed afterdepolarization (EAD and DAD)-induced triggered activity.
objectiveTo evaluate the electrophysiological properties of GS-458967 (GS967), a potent and highly selective late INa blocker, in canine Purkinje fibers (PFs) and pulmonary vein (PV) and superior vena cava (SVC) sleeve preparations.
methodsTransmembrane action potentials were recorded from canine PFs and PV and SVC sleeve preparations by using standard microelectrode techniques. The rapidly activating delayed rectifier potassium channel current blocker E-4031 (2.5-5 µM) and the late INa agonist ATX-II (10 nM) were used to induce EADs in PFs. Isoproterenol (1 µM), high calcium ([Ca(2+)]o = 5.4 mM), or their combination was used to induce DADs and triggered activity.
resultsIn PFs, GS967 (10-300 nM) caused a significant concentration-dependent reduction in action potential duration without altering the maximum rate of rise of the action potential upstroke, action potential amplitude, or resting membrane potential at any rate studied (basic cycle lengths of 1000, 500, and 300 ms) or concentration evaluated (n = 5; P < .05). GS967 (30-100 nM) abolished EADs and EAD-induced triggered activity elicited in PFs by exposure to E-4031 (n = 4) or ATX-II (n = 4). In addition, GS967 reduced or abolished DADs and suppressed DAD-induced triggered activity elicited in PFs (n = 4) and PV (n = 4) and SVC (n = 3) sleeve preparations by exposure to isoproterenol, high calcium, or their combination.
conclusionsOur data suggest that the selective inhibition of late INa with GS967 can exert antiarrhythmic effects by suppressing EAD- and DAD-mediated extrasystolic activity in PFs and PV and SVC sleeve preparations.
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Registered trials
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