Key result
A mathematical model with two slow gating variables revealed that early afterdepolarizations in cardiac action potentials arise as mixed mode oscillations due to a folded node singularity.
Why the study?
The onset of early afterdepolarizations had previously been studied using action potential models with only one slow ion channel gating variable, motivating analysis using dynamical systems with two slow gating variables.
Population
Mathematical cardiac action potential models with two slow gating variables
Comparison
Folded node analysis and full system bifurcation analysis
Design
Mathematical modeling and computational simulation study
Authors
Loading...
May inform CiPA arrhythmia risk assessment; hypothesis-generating for EAD mechanisms and requires experimental validation.
The study identifies a folded node singularity as a novel mechanism for early afterdepolarizations and proposes a computational risk metric for estimating a drug's proarrhythmic liability.
Kügler et al. (2018) studied Early afterdepolarizations (EADs) and cardiac arrhythmias. Mathematical modeling of cardiac action potentials (two slow gating variables) vs. Standard fast-slow analysis (one slow variable) was evaluated on Mechanism of EADs genesis and parameter regions of EADs occurrence. A mathematical model with two slow gating variables revealed that early afterdepolarizations in cardiac action potentials arise as mixed mode oscillations due to a folded node singularity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: