ArticleAmerican journal of physiology. Heart and circulatory physiology2011
Ca²⁺-induced delayed afterdepolarizations are triggered by dyadic subspace Ca2²⁺ affirming that increasing SERCA reduces aftercontractions.
Article in American journal of physiology. Heart and circulatory physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Insights in ischemia/reperfusion injury and cardioprotection: neglected and emerging pathways and therapeutic targets for a personalized therapy.Basic research in cardiology · 2026Review
- Central autonomic network dysfunction in Stroke-Heart Syndrome: mechanistic roles of the insula and limbic system.Frontiers in neuroscience · 2026Review
- Abnormal calcium release and delayed afterdepolarizations: A comparison of two mathematical models for human ventricular myocytes.PloS one · 2026Article
- KFrontiers in physiology · 2025Article
- An hiPSC-CM approach for electrophysiological phenotyping of a patient-specific case of short-coupled TdP.Stem cell research & therapy · 2024Article
- Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2024Review
- Stress-Induced Proteasome Sub-Cellular Translocation in Cardiomyocytes Causes Altered Intracellular Calcium Handling and Arrhythmias.International journal of molecular sciences · 2024Article
- Mechanisms of pulmonary arterial hypertension-induced atrial fibrillation: insights from multi-scale models of the human atria.Interface focus · 2023Article
- Estimating the probability of early afterdepolarizations and predicting arrhythmic risk associated with long QT syndrome type 1 mutations.Biophysical journal · 2023Article
- Bacterial toxins and heart function: heat-labileBiophysical reviews · 2023Article
- Constitutively Activating GNAS Somatic Mutation in Right Ventricular Outflow Tract Tachycardia.Circulation. Arrhythmia and electrophysiology · 2021Article
- Estimating ectopic beat probability with simplified statistical models that account for experimental uncertainty.PLoS computational biology · 2021Article
- Review
- Implications of SGLT Inhibition on Redox Signalling in Atrial Fibrillation.International journal of molecular sciences · 2021Review
- Calibration of ionic and cellular cardiac electrophysiology models.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- 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
- Human Purkinje in silico model enables mechanistic investigations into automaticity and pro-arrhythmic abnormalities.Journal of molecular and cellular cardiology · 2020Article
- In silico investigation of the mechanisms underlying atrial fibrillation due to impaired Pitx2.PLoS computational biology · 2020Article
- Simulation of the Effects of Extracellular Calcium Changes Leads to a Novel Computational Model of Human Ventricular Action Potential With a Revised Calcium Handling.Frontiers in physiology · 2020Article
- Targeting CaFrontiers in physiology · 2020Review
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3 authors.
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Abstract
Ca(2+)-induced delayed afterdepolarizations (DADs) are depolarizations that occur after full repolarization. They have been observed across multiple species and cell types. Experimental results have indicated that the main cause of DADs is Ca(2+) overload. The main hypothesis as to their initiation has been Ca(2+) overflow from the overloaded sarcoplasmic reticulum (SR). Our results using 37 previously published mathematical models provide evidence that Ca(2+)-induced DADs are initiated by the same mechanism as Ca(2+)-induced Ca(2+) release, i.e., the modulation of the opening of ryanodine receptors (RyR) by Ca(2+) in the dyadic subspace; an SR overflow mechanism was not necessary for the induction of DADs in any of the models. The SR Ca(2+) level is better viewed as a modulator of the appearance of DADs and the magnitude of Ca(2+) release. The threshold for the total Ca(2+) level within the cell (not only the SR) at which Ca(2+) oscillations arise in the models is close to their baseline level (∼1- to 3-fold). It is most sensitive to changes in the maximum sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) pump rate (directly proportional), the opening probability of RyRs, and the Ca(2+) diffusion rate from the dyadic subspace into the cytosol (both indirectly proportional), indicating that the appearance of DADs is multifactorial. This shift in emphasis away from SR overload as the trigger for DADs toward a multifactorial analysis could explain why SERCA overexpression has been shown to suppress DADs (while increasing contractility) and why DADs appear during heart failure (at low SR Ca(2+) levels).
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