ArticleJournal of molecular and cellular cardiology2010
A novel computational model of the human ventricular action potential and Ca transient.
Article in Journal of molecular and cellular cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 papers.
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Who cites it
253 citing papers in PubMed.
- Gradient-based parameter optimization method to determine membrane ionic current composition in human induced pluripotent stem cell-derived cardiomyocytes.Scientific reports · 2022Trial
- Interplay between store-operated calcium entry and mitochondrial phosphate handling modulates force and fatigue during exercise.The Journal of physiology · 2026Article
- In silico modelling of multi-electrode arrays for enhancing cardiac drug testing on hiPSC-CM heterogeneous tissues.The Journal of physiology · 2026Article
- Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation.The Journal of physiology · 2026Review
- Modes of onset of ventricular arrhythmias in J-wave syndromes: mechanistic insights from computational modeling.American journal of physiology. Heart and circulatory physiology · 2026Article
- T-World Virtual Human Cardiomyocyte. I. Development, Validation, and Cell Arrhythmogenesis.Circulation research · 2026Article
- Accurate computation of ionic concentrations in the synaptic cleft requires the full Poisson-Nernst-Planck (PNP) equations.PLoS computational biology · 2026Article
- A model for the human fetal ventricular myocyte electrophysiology.PLoS computational biology · 2026Article
- Toward Standardized Methodologies for Drug-Induced Proarrhythmia Classification: An In Silico Proof of Concept.Computational and structural biotechnology journal · 2026Article
- Development and Clinical Validation of a Cross-Sex Translator of ECG Drug Responses.JACC. Clinical electrophysiology · 2025Article
- Compromised repolarization reserve in a murine model of catecholaminergic polymorphic ventricular tachycardia caused by RyR2-R420Q mutation.Journal of molecular and cellular cardiology · 2025Article
- A simulation study on the role of mitochondria-sarcoplasmic reticulum CaThe Journal of physiology · 2025Article
- Review
- Comparative analysis of the ten Tusscher and Tomek human ventricular cell models at cellular, tissue, and organ levels: Implications for post-infarct ventricular tachycardia simulation.Physiological reports · 2025Article
- Comparison of in silico predictions of action potential duration in response to inhibition of IKr and ICaL with new human ex vivo recordings.PLoS computational biology · 2025Article
- Electrodiffusion dynamics in the cardiomyocyte dyad at nano-scale resolution using the Poisson-Nernst-Planck (PNP) equations.PLoS computational biology · 2025Article
- Developing cardiac digital twin populations powered by machine learning provides electrophysiological insights in conduction and repolarization.Nature cardiovascular research · 2025Article
- Exploring the mechanisms of sex-specific proarrhythmia in long QT syndrome through computational modeling.American journal of physiology. Heart and circulatory physiology · 2025Article
- T-World: A highly general computational model of a human ventricular myocyte.bioRxiv : the preprint server for biology · 2025Article
- Modeling Fibroblast-Cardiomyocyte Interactions: Unveiling the Role of Ion Currents in Action Potential Modulation.International journal of molecular sciences · 2024Article
193 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors.
Funding
Abstract
We have developed a detailed mathematical model for Ca handling and ionic currents in the human ventricular myocyte. Our aims were to: (1) simulate basic excitation-contraction coupling phenomena; (2) use realistic repolarizing K current densities; (3) reach steady-state. The model relies on the framework of the rabbit myocyte model previously developed by our group, with subsarcolemmal and junctional compartments where ion channels sense higher [Ca] vs. bulk cytosol. Ion channels and transporters have been modeled on the basis of the most recent experimental data from human ventricular myocytes. Rapidly and slowly inactivating components of I(to) have been formulated to differentiate between endocardial and epicardial myocytes. Transmural gradients of Ca handling proteins and Na pump were also simulated. The model has been validated against a wide set of experimental data including action potential duration (APD) adaptation and restitution, frequency-dependent increase in Ca transient peak and [Na](i). Interestingly, Na accumulation at fast heart rate is a major determinant of APD shortening, via outward shifts in Na pump and Na-Ca exchange currents. We investigated the effects of blocking K currents on APD and repolarization reserve: I(Ks) block does not affect the former and slightly reduces the latter; I(K1) blockade modestly increases APD and more strongly reduces repolarization reserve; I(Kr) blockers significantly prolong APD, an effect exacerbated as pacing frequency is decreased, in good agreement with experimental results in human myocytes. We conclude that this model provides a useful framework to explore excitation-contraction coupling mechanisms and repolarization abnormalities at the single myocyte level.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.