ReviewJournal of molecular and cellular cardiology2012
Pathophysiology of the cardiac late Na current and its potential as a drug target.
Review in Journal of molecular and cellular cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Istaroxime in Acute Heart Failure and Early Cardiogenic Shock: A Calcium-Cycling Approach to Inotropic Therapy.International journal of molecular sciences · 2026Review
- Mutation-specific roles of sustained sodium current (IPNAS nexus · 2025Article
- Mechanisms of Chemical Atrial Defibrillation by Flecainide and Ibutilide.JACC. Clinical electrophysiology · 2024Article
- Phosphorylation of cardiac sodium channel at Ser571 anticipates manifestations of the aging myopathy.American journal of physiology. Heart and circulatory physiology · 2024Article
- Chronic Mexiletine Administration Increases Sodium Current in Non-Diseased Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Biomedicines · 2024Article
- Exploring mutation specific beta blocker pharmacology of the pathogenic late sodium channel current from patient-specific pluripotent stem cell myocytes derived from long QT syndrome mutation carriers.Channels (Austin, Tex.) · 2022Article
- Article
- Effects of Antiarrhythmic Drugs on Antiepileptic Drug Action-A Critical Review of Experimental Findings.International journal of molecular sciences · 2022Review
- 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
- Cardiac Late Sodium Channel Current Is a Molecular Target for the Sodium/Glucose Cotransporter 2 Inhibitor Empagliflozin.Circulation · 2021Article
- Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression.International journal of molecular sciences · 2021Article
- Diabetes-induced changes in cardiac voltage-gated ion channels.World journal of diabetes · 2021Review
- Protective Effects of Spermidine and Melatonin on Deltamethrin-Induced Cardiotoxicity and Neurotoxicity in Zebrafish.Cardiovascular toxicology · 2021Article
- Fibroblast growth factor homologous factors tune arrhythmogenic late NaV1.5 current in calmodulin binding-deficient channels.JCI insight · 2020Article
- Modulation of the cardiac sodium channel NaJournal of molecular and cellular cardiology · 2020Article
- Hyponatremia and Cancer Progression: Possible Association with Sodium-Transporting Proteins.Bioelectricity · 2020Article
- Super-Resolution Imaging Using a Novel High-Fidelity Antibody Reveals Close Association of the Neuronal Sodium Channel NaMicroscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada · 2020Article
- Ranolazine as an Alternative Therapy to Flecainide for SCN5A V411M Long QT Syndrome Type 3 Patients.Frontiers in pharmacology · 2020Article
- Modifications of sodium channel voltage dependence induce arrhythmia-favouring dynamics of cardiac action potentials.PloS one · 2020Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
A pathological increase in the late component of the cardiac Na(+) current, I(NaL), has been linked to disease manifestation in inherited and acquired cardiac diseases including the long QT variant 3 (LQT3) syndrome and heart failure. Disruption in I(NaL) leads to action potential prolongation, disruption of normal cellular repolarization, development of arrhythmia triggers, and propensity to ventricular arrhythmia. Attempts to treat arrhythmogenic sequelae from inherited and acquired syndromes pharmacologically with common Na(+) channel blockers (e.g. flecainide, lidocaine, and amiodarone) have been largely unsuccessful. This is due to drug toxicity and the failure of most current drugs to discriminate between the peak current component, chiefly responsible for single cell excitability and propagation in coupled tissue, and the late component (I(NaL)) of the Na(+) current. Although small in magnitude as compared to the peak Na(+) current (~1-3%), I(NaL) alters action potential properties and increases Na(+) loading in cardiac cells. With the increasing recognition that multiple cardiac pathological conditions share phenotypic manifestations of I(NaL) upregulation, there has been renewed interest in specific pharmacological inhibition of I(Na). The novel antianginal agent ranolazine, which shows a marked selectivity for late versus peak Na(+) current, may represent a novel drug archetype for targeted reduction of I(NaL). This article aims to review common pathophysiological mechanisms leading to enhanced I(NaL) in LQT3 and heart failure as prototypical disease conditions. Also reviewed are promising therapeutic strategies tailored to alter the molecular mechanisms underlying I(Na) mediated arrhythmia triggers.
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