ArticlePloS one2012
Simulation and mechanistic investigation of the arrhythmogenic role of the late sodium current in human heart failure.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 77 citations in OpenAlex.
- Late IMedicinal research reviews · 2026Review
- Reduced gap junction coupling amplifies the effects of cardiomyocyte variability and destabilizes the heartbeat.Physiological reports · 2025Article
- An Electromechanical Model-Based Study on the Dosage Effects of Ranolazine in Treating Failing HCM Cardiomyocyte.Cellular and molecular bioengineering · 2025Article
- Role of NaInternational journal of molecular sciences · 2024Review
- Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.Physiological reviews · 2024Review
- Late Sodium Current of the Heart: Where Do We Stand and Where Are We Going?Pharmaceuticals (Basel, Switzerland) · 2022Review
- Protective Effect of Trimetazidine on Potassium Ion Homeostasis in Myocardial Tissue in Mice with Heart Failure.BioMed research international · 2022Article
- Discussion on Repolarization Reserve between Patients with Coronary Heart Disease and Normal Controls.Computational and mathematical methods in medicine · 2022Article
- Pro-Arrhythmic Effects of Discontinuous Conduction at the Purkinje Fiber-Ventricle Junction Arising From Heart Failure-Induced Ionic Remodeling - Insights From Computational Modelling.Frontiers in physiology · 2022Article
- Late ICirculation. Arrhythmia and electrophysiology · 2020Article
- Quantitative analysis of variability in an integrated model of human ventricular electrophysiology and β-adrenergic signaling.Journal of molecular and cellular cardiology · 2020Article
- Ranolazine as an Alternative Therapy to Flecainide for SCN5A V411M Long QT Syndrome Type 3 Patients.Frontiers in pharmacology · 2020Article
- Late Sodium Current Inhibitors as Potential Antiarrhythmic Agents.Frontiers in pharmacology · 2020Review
- Paradoxical Onset of Arrhythmic Waves from Depolarized Areas in Cardiac Tissue Due to Curvature-Dependent Instability.Physical review. X · 2018Article
- Sensitivity analysis of ventricular activation and electrocardiogram in tailored models of heart-failure patients.Medical & biological engineering & computing · 2018Article
- CaFrontiers in physiology · 2018Article
- Sensitivity analysis revealing the effect of modulating ionic mechanisms on calcium dynamics in simulated human heart failure.PloS one · 2017Article
- A mathematical model for active contraction in healthy and failing myocytes and left ventricles.PloS one · 2017Article
- Illuminating Myocyte-Fibroblast Homotypic and Heterotypic Gap Junction Dynamics Using Dynamic Clamp.Biophysical journal · 2016Article
- Reduced response to IKr blockade and altered hERG1a/1b stoichiometry in human heart failure.Journal of molecular and cellular cardiology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heart failure constitutes a major public health problem worldwide. The electrophysiological remodeling of failing hearts sets the stage for malignant arrhythmias, in which the role of the late Na(+) current (I(NaL)) is relevant and is currently under investigation. In this study we examined the role of I(NaL) in the electrophysiological phenotype of ventricular myocytes, and its proarrhythmic effects in the failing heart. A model for cellular heart failure was proposed using a modified version of Grandi et al. model for human ventricular action potential that incorporates the formulation of I(NaL). A sensitivity analysis of the model was performed and simulations of the pathological electrical activity of the cell were conducted. The proposed model for the human I(NaL) and the electrophysiological remodeling of myocytes from failing hearts accurately reproduce experimental observations. The sensitivity analysis of the modulation of electrophysiological parameters of myocytes from failing hearts due to ion channels remodeling, revealed a role for I(NaL) in the prolongation of action potential duration (APD), triangulation of the shape of the AP, and changes in Ca(2+) transient. A mechanistic investigation of intracellular Na(+) accumulation and APD shortening with increasing frequency of stimulation of failing myocytes revealed a role for the Na(+)/K(+) pump, the Na(+)/Ca(2+) exchanger and I(NaL). The results of the simulations also showed that in failing myocytes, the enhancement of I(NaL) increased the reverse rate-dependent APD prolongation and the probability of initiating early afterdepolarizations. The electrophysiological remodeling of failing hearts and especially the enhancement of the I(NaL) prolong APD and alter Ca(2+) transient facilitating the development of early afterdepolarizations. An enhanced I(NaL) appears to be an important contributor to the electrophysiological phenotype and to the dysregulation of [Ca(2+)](i) homeostasis of failing myocytes.
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