ArticleJournal of molecular and cellular cardiology2016
There and back again: Iterating between population-based modeling and experiments reveals surprising regulation of calcium transients in rat cardiac myocytes.
Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Investigational Treatments for COVID-19 may Increase Ventricular Arrhythmia Risk Through Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2021Article
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- Heart failure-induced atrial remodelling promotes electrical and conduction alternans.PLoS computational biology · 2020Article
- Afterdepolarizations and abnormal calcium handling in atrial myocytes with modulated SERCA uptake: a sensitivity analysis of calcium handling channels.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2020Article
- Quantitative analysis of variability in an integrated model of human ventricular electrophysiology and β-adrenergic signaling.Journal of molecular and cellular cardiology · 2020Article
- Investigational treatments for COVID-19 may increase ventricular arrhythmia risk through drug interactions.medRxiv : the preprint server for health sciences · 2020Article
- Dimensions of control for subthreshold oscillations and spontaneous firing in dopamine neurons.PLoS computational biology · 2019Article
- Visualization of currents in neural models with similar behavior and different conductance densities.eLife · 2019Article
- Global Sensitivity Analysis of Ventricular Myocyte Model-Derived Metrics for Proarrhythmic Risk Assessment.Frontiers in pharmacology · 2019Article
- Slow Delayed Rectifier Current Protects Ventricular Myocytes From Arrhythmic Dynamics Across Multiple Species: A Computational Study.Circulation. Arrhythmia and electrophysiology · 2018Article
- The CaeLife · 2018Article
- A privileged role for neuronal NaThe Journal of general physiology · 2018Article
- Computational modeling of amylin-induced calcium dysregulation in rat ventricular cardiomyocytes.Cell calcium · 2018Article
- A Heart for Diversity: Simulating Variability in Cardiac Arrhythmia Research.Frontiers in physiology · 2018Review
- Population-based mechanistic modeling allows for quantitative predictions of drug responses across cell types.NPJ systems biology and applications · 2018Article
- Revealing kinetics and state-dependent binding properties of IChaos (Woodbury, N.Y.) · 2017Article
- Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.The Journal of physiology · 2017Article
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- Logistic regression analysis of populations of electrophysiological models to assess proarrythmic risk.MethodsX · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
While many ion channels and transporters involved in cardiac cellular physiology have been identified and described, the relative importance of each in determining emergent cellular behaviors remains unclear. Here we address this issue with a novel approach that combines population-based mathematical modeling with experimental tests to systematically quantify the relative contributions of different ion channels and transporters to the amplitude of the cellular Ca(2+) transient. Sensitivity analysis of a mathematical model of the rat ventricular cardiomyocyte quantified the response of cell behaviors to changes in the level of each ion channel and transporter, and experimental tests of these predictions were performed to validate or invalidate the predictions. The model analysis found that partial inhibition of the transient outward current in rat ventricular epicardial myocytes was predicted to have a greater impact on Ca(2+) transient amplitude than either: (1) inhibition of the same current in endocardial myocytes, or (2) comparable inhibition of the sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA). Experimental tests confirmed the model predictions qualitatively but showed some quantitative disagreement. This guided us to recalibrate the model by adjusting the relative importance of several Ca(2+) fluxes, thereby improving the consistency with experimental data and producing a more predictive model. Analysis of human cardiomyocyte models suggests that the relative importance of outward currents to Ca(2+) transporters is generalizable to human atrial cardiomyocytes, but not ventricular cardiomyocytes. Overall, our novel approach of combining population-based mathematical modeling with experimental tests has yielded new insight into the relative importance of different determinants of cell behavior.
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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.