ArticleCirculation. Arrhythmia and electrophysiology2015
Slow [Na]i Changes and Positive Feedback Between Membrane Potential and [Ca]i Underlie Intermittent Early Afterdepolarizations and Arrhythmias.
Article in Circulation. Arrhythmia and electrophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Multiscale stochastic modeling for calcium dynamics in cardiac electrophysiology: assessing whole-cell model reliability under phosphorylation and LCC downregulation.Frontiers in network physiology · 2026Article
- Intracellular ion accumulation in the genesis of complex action potential dynamics under cardiac diseases.Physical review. E · 2024Article
- Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.Biomolecules · 2022Review
- Intracellular NaInternational journal of molecular sciences · 2021Article
- A Novel Computational Model of the Rabbit Atrial Cardiomyocyte With Spatial Calcium Dynamics.Frontiers in physiology · 2020Article
- Bifurcations Caused by Feedback between Voltage and Intracellular Ion Concentrations in Ventricular Myocytes.Physical review letters · 2019Article
- Integrative and theoretical research on the architecture of a biological system and its disorder.The journal of physiological sciences : JPS · 2019Review
- Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the NaWiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model:Frontiers in physiology · 2019Article
- Control of voltage-driven instabilities in cardiac myocytes with memory.Chaos (Woodbury, N.Y.) · 2018Article
- Memory-induced nonlinear dynamics of excitation in cardiac diseases.Physical review. E · 2018Article
- Hysteretic Dynamics of Multi-Stable Early Afterdepolarisations with Repolarisation Reserve Attenuation: A Potential Dynamical Mechanism for Cardiac Arrhythmias.Scientific reports · 2017Article
- Global Optimization of Ventricular Myocyte Model to Multi-Variable Objective Improves Predictions of Drug-Induced Torsades de Pointes.Frontiers in physiology · 2017Article
- Anti-arrhythmic strategies for atrial fibrillation: The role of computational modeling in discovery, development, and optimization.Pharmacology & therapeutics · 2016Review
- Mechanisms of cardiac arrhythmias.Journal of arrhythmia · 2016Review
- Reactive Oxygen Species, Endoplasmic Reticulum Stress and Mitochondrial Dysfunction: The Link with Cardiac Arrhythmogenesis.Frontiers in physiology · 2016Review
- Altered Calcium Handling and Ventricular Arrhythmias in Acute Ischemia.Clinical Medicine Insights. Cardiology · 2016Review
- Molecular and Electrophysiological Mechanisms Underlying Cardiac Arrhythmogenesis in Diabetes Mellitus.Journal of diabetes research · 2016Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMost cardiac arrhythmias occur intermittently. As a cellular precursor of lethal cardiac arrhythmias, early afterdepolarizations (EADs) during action potentials(APs) have been extensively investigated, and mechanisms for the occurrence of EADs on a beat-to-beat basis have been proposed. However, no previous study explains slow fluctuations in EADs, which may underlie intermittency of EAD trains and consequent arrhythmias. We hypothesize that the feedback of intracellular calcium and sodium concentrations ([Na](i) and [Ca](i)) that influence membrane voltage (V) can explain EAD intermittency. METHODS AND
resultsAP recordings in rabbit ventricular myocytes revealed intermittent EADs, with slow fluctuations between runs of APs with EADs present or absent. We then used dynamical systems analysis and detailed mathematical models of rabbit ventricular myocytes that replicate the observed behavior and investigated the underlying mechanism. We found that a dominance of inward Na-Ca exchanger current (I(NCX)) over Ca-dependent inactivation of L-type Ca current (I(CaL)) forms a positive feedback between [Ca](i) and V, thus resulting in 2 stable AP states, with and without EADs (ie, bistability). Slow changes in [Na](i) determine the transition between these 2 states, forming a bistable on-off switch of EADs. Tissue simulations showed that this bistable switch of cellular EADs provided both a trigger and a functional substrate for intermittent arrhythmias in homogeneous tissues.
conclusionsOur study demonstrates that the interaction among V, [Ca](i), and [Na](i) causes slow on-off switching (or bistability) of AP duration in cardiac myocytes and EAD-mediated arrhythmias and suggests a novel possible mechanism for intermittency of cardiac arrhythmias.
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