ArticleThe Journal of physiology2017
Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.
Article in The Journal of physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- The electrophysiology of ventricular cell pairs.Pflugers Archiv : European journal of physiology · 2025Review
- Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.PLoS computational biology · 2024Article
- Electrophysiological Mechanism of Catestatin Antiarrhythmia: Enhancement ofJournal of the American Heart Association · 2024Article
- Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.bioRxiv : the preprint server for biology · 2024Article
- Computational design of custom therapeutic cells to correct failing human cardiomyocytes.Frontiers in systems biology · 2023Article
- Antiarrhythmic calcium channel blocker verapamil inhibits trek currents in sympathetic neurons.Frontiers in pharmacology · 2022Article
- Calcium dysregulation increases right ventricular outflow tract arrhythmogenesis in rabbit model of chronic kidney disease.Journal of cellular and molecular medicine · 2021Article
- Prediction of arrhythmia susceptibility through mathematical modeling and machine learning.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Certain beta blockers (e.g., bisoprolol) may be reevaluated in hypertension guidelines for patients with left ventricular hypertrophy to diminish the ventricular arrhythmic risk.Journal of human hypertension · 2021Review
- Characterization of the Electrophysiologic Remodeling of Patients With Ischemic Cardiomyopathy by Clinical Measurements and Computer Simulations Coupled With Machine Learning.Frontiers in physiology · 2021Article
- Sensitivity Analysis of Ion Channel Conductance on Myocardial Electromechanical Delay: Computational Study.Frontiers in physiology · 2021Article
- Calibration of ionic and cellular cardiac electrophysiology models.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Quantitative analysis of variability in an integrated model of human ventricular electrophysiology and β-adrenergic signaling.Journal of molecular and cellular cardiology · 2020Article
- Antiarrhythmic mechanisms of beta blocker therapy.Pharmacological research · 2019Review
- Dynamic clamping human and rabbit atrial calcium current: narrowing IThe Journal of physiology · 2019Article
- Global Sensitivity Analysis of Ventricular Myocyte Model-Derived Metrics for Proarrhythmic Risk Assessment.Frontiers in pharmacology · 2019Article
- Light-Activated Dynamic Clamp Using iPSC-Derived Cardiomyocytes.Biophysical journal · 2018Article
- Slow Delayed Rectifier Current Protects Ventricular Myocytes From Arrhythmic Dynamics Across Multiple Species: A Computational Study.Circulation. Arrhythmia and electrophysiology · 2018Article
- Description of the Human Atrial Action Potential Derived From a Single, Congruent Data Source: Novel Computational Models for Integrated Experimental-Numerical Study of Atrial Arrhythmia Mechanisms.Frontiers in physiology · 2018Article
- A Heart for Diversity: Simulating Variability in Cardiac Arrhythmia Research.Frontiers in physiology · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
key pointsArrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. ABSTRACT: Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K
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Registered trials
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.