ArticleBiophysical journal2005
Dynamical mechanisms of pacemaker generation in IK1-downregulated human ventricular myocytes: insights from bifurcation analyses of a mathematical model.
Article in Biophysical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- Mechanisms of fever-induced QT prolongation and torsades de pointes in patients with KCNH2 mutation.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Article
- Sensitivity Analysis of Cardiac Alternans and Tachyarrhythmia to Ion Channel Conductance Using Population Modeling.Bioengineering (Basel, Switzerland) · 2022Article
- Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.Biomolecules · 2022Review
- Quantitative roles of ion channel dynamics on ventricular action potential.Channels (Austin, Tex.) · 2021Article
- Reciprocal interaction between IK1 and If in biological pacemakers: A simulation study.PLoS computational biology · 2021Article
- Mechanisms underlying pro-arrhythmic abnormalities arising from Pitx2-induced electrical remodelling: an in silico intersubject variability study.Annals of translational medicine · 2021Article
- Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases.Cardiovascular research · 2020Article
- Biological pacemaker: from biological experiments to computational simulation.Journal of Zhejiang University. Science. B · 2020Review
- A compartmentalized mathematical model of mouse atrial myocytes.American journal of physiology. Heart and circulatory physiology · 2020Article
- A Simulation Study on the Pacing and Driving of the Biological Pacemaker.BioMed research international · 2020Article
- The Cardiac Pacemaker Story-Fundamental Role of the NaFrontiers in pharmacology · 2020Review
- Integrative and theoretical research on the architecture of a biological system and its disorder.The journal of physiological sciences : JPS · 2019Review
- Multiple Dynamical Mechanisms of Phase-2 Early Afterdepolarizations in a Human Ventricular Myocyte Model:Frontiers in physiology · 2019Article
- Determinants of early afterdepolarization properties in ventricular myocyte models.PLoS computational biology · 2018Article
- Ionic and cellular mechanisms underlying TBX5/PITX2 insufficiency-induced atrial fibrillation: Insights from mathematical models of human atrial cells.Scientific reports · 2018Article
- A Heart for Diversity: Simulating Variability in Cardiac Arrhythmia Research.Frontiers in physiology · 2018Review
- Hysteretic Dynamics of Multi-Stable Early Afterdepolarisations with Repolarisation Reserve Attenuation: A Potential Dynamical Mechanism for Cardiac Arrhythmias.Scientific reports · 2017Article
- Electrophysiological properties of iPS cell-derived cardiomyocytes from a patient with long QT syndrome type 1 harboring the novel mutation M437V of KCNQ1.Regenerative therapy · 2016Article
- Quantitative Decomposition of Dynamics of Mathematical Cell Models: Method and Application to Ventricular Myocyte Models.PloS one · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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Abstract
Dynamical mechanisms of the biological pacemaker (BP) generation in human ventricular myocytes were investigated by bifurcation analyses of a mathematical model. Equilibrium points (EPs), periodic orbits, stability of EPs, and bifurcation points were determined as functions of bifurcation parameters, such as the maximum conductance of inward-rectifier K+ current (I(K1)), for constructing bifurcation diagrams. Stable limit cycles (BP activity) abruptly appeared around an unstable EP via a saddle-node bifurcation when I(K1) was suppressed by 84.6%. After the bifurcation at which a stable EP disappears, the I(K1)-reduced system has an unstable EP only, which is essentially important for stable pacemaking. To elucidate how individual sarcolemmal currents contribute to EP instability and BP generation, we further explored the bifurcation structures of the system during changes in L-type Ca2+ channel current (I(Ca,L)), delayed-rectifier K+ currents (I(K)), or Na(+)/Ca2+ exchanger current (I(NaCa)). Our results suggest that 1), I(Ca,L) is, but I(K) or I(NaCa) is not, responsible for EP instability as a requisite to stable BP generation; 2), I(K) is indispensable for robust pacemaking with large amplitude, high upstroke velocity, and stable frequency; and 3), I(NaCa) is the dominant pacemaker current but is not necessarily required for the generation of spontaneous oscillations.
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