ArticlePloS one2016
Experimentally-Based Computational Investigation into Beat-To-Beat Variability in Ventricular Repolarization and Its Response to Ionic Current Inhibition.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Parameter inference for stochastic reaction models of ion channel gating from whole-cell voltage-clamp data.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2025Article
- The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity.International journal of molecular sciences · 2024Review
- Cell-to-cell heterogeneity in ion channel conductance impacts substrate vulnerability to arrhythmia.American journal of physiology. Heart and circulatory physiology · 2024Article
- Inducing IJournal of molecular and cellular cardiology · 2022Article
- Prediction of arrhythmia susceptibility through mathematical modeling and machine learning.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis.Frontiers in physiology · 2019Article
- Complex Interaction Between Low-Frequency APD Oscillations and Beat-to-Beat APD Variability in Humans Is Governed by the Sympathetic Nervous System.Frontiers in physiology · 2019Article
- From ionic to cellular variability in human atrial myocytes: an integrative computational and experimental study.American journal of physiology. Heart and circulatory physiology · 2018Article
- Editorial: Safety Pharmacology - Risk Assessment QT Interval Prolongation and Beyond.Frontiers in physiology · 2018Article
- Article
- Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans.Frontiers in physiology · 2018Article
- Integrating cardiomyocytes from human pluripotent stem cells in safety pharmacology: has the time come?British journal of pharmacology · 2017Review
- β-Adrenergic receptor stimulation inhibits proarrhythmic alternans in postinfarction border zone cardiomyocytes: a computational analysis.American journal of physiology. Heart and circulatory physiology · 2017Article
- Modelling variability in cardiac electrophysiology: a moment-matching approach.Journal of the Royal Society, Interface · 2017Article
- Humans Vary, So Cardiac Models Should Account for That Too!Frontiers in physiology · 2017Review
- Autonomic Modulation in Patients with Heart Failure Increases Beat-to-Beat Variability of Ventricular Action Potential Duration.Frontiers in physiology · 2017Article
- A new hERG allosteric modulator rescues genetic and drug-induced long-QT syndrome phenotypes in cardiomyocytes from isogenic pairs of patient induced pluripotent stem cells.EMBO molecular medicine · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Beat-to-beat variability in repolarization (BVR) has been proposed as an arrhythmic risk marker for disease and pharmacological action. The mechanisms are unclear but BVR is thought to be a cell level manifestation of ion channel stochasticity, modulated by cell-to-cell differences in ionic conductances. In this study, we describe the construction of an experimentally-calibrated set of stochastic cardiac cell models that captures both BVR and cell-to-cell differences in BVR displayed in isolated canine action potential measurements using pharmacological agents. Simulated and experimental ranges of BVR are compared in control and under pharmacological inhibition, and the key ionic currents determining BVR under physiological and pharmacological conditions are identified. Results show that the 4-aminopyridine-sensitive transient outward potassium current, Ito1, is a fundamental driver of BVR in control and upon complete inhibition of the slow delayed rectifier potassium current, IKs. In contrast, IKs and the L-type calcium current, ICaL, become the major contributors to BVR upon inhibition of the fast delayed rectifier potassium current, IKr. This highlights both IKs and Ito1 as key contributors to repolarization reserve. Partial correlation analysis identifies the distribution of Ito1 channel numbers as an important independent determinant of the magnitude of BVR and drug-induced change in BVR in control and under pharmacological inhibition of ionic currents. Distributions in the number of IKs and ICaL channels only become independent determinants of the magnitude of BVR upon complete inhibition of IKr. These findings provide quantitative insights into the ionic causes of BVR as a marker for repolarization reserve, both under control condition and pharmacological inhibition.
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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.