ArticlePloS one2018
Early afterdepolarizations in cardiac action potentials as mixed mode oscillations due to a folded node singularity.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Mixed-mode oscillations in a three-timescale coupled Morris-Lecar system.Chaos (Woodbury, N.Y.) · 2024Article
- Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.Biomolecules · 2022Review
- Circadian Rhythms of Early Afterdepolarizations and Ventricular Arrhythmias in a Cardiomyocyte Model.Biophysical journal · 2021Article
- Canard analysis reveals why a large Ca2+ window current promotes early afterdepolarizations in cardiac myocytes.PLoS computational biology · 2020Article
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3 authors.
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Abstract
Early afterdepolarizations (EADs) are pathological voltage oscillations during the repolarization phase of cardiac action potentials. They are considered as potential precursors to cardiac arrhythmias and have recently gained much attention in the context of preclinical drug safety testing under the Comprehensive in vitro Proarrhythmia Assay (CiPA) paradigm. From the viewpoint of multiple time scales theory, the onset of EADs has previously been studied by means of mathematical action potential models with one slow ion channel gating variable. In this article, we for the first time associate EADs with mixed mode oscillations in dynamical systems with two slow gating variables and present a folded node singularity of the slow flow as a novel mechanism for EADs genesis. We derive regions of the pharmacology parameter space in which EADs occur using both the folded node analysis and a full system bifurcation analysis, and we suggest the normal distance to the boundary of the EADs region as a mechanism-based risk metric to computationally estimate a drug's proarrhythmic liability.
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