ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2022
Increased SERCA2a sub-cellular heterogeneity in right-ventricular heart failure inhibits excitation-contraction coupling and modulates arrhythmogenic dynamics.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- DENND3-p.R534S disrupts dyadic microdomain architecture to drive potentially pro-arrhythmic calcium and electrophysiologic instability.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Type I collagen-targeted liposome delivery of Serca2a modulates myocardium calcium homeostasis and reduces cardiac fibrosis induced by myocardial infarction.Materials today. Bio · 2024Article
- Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.Physiological reviews · 2024Review
- Patchy fibrosis promotes trigger-substrate interactions that both generate and maintain atrial fibrillation.Interface focus · 2023Article
- Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease.Open biology · 2023Article
- Efficacy of the New Inotropic Agent Istaroxime in Acute Heart Failure.Journal of clinical medicine · 2022Review
- New revelations on the interplay between cardiomyocyte architecture and cardiomyocyte function in growth, health, and disease: a brief introduction.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- Increased SERCA2a sub-cellular heterogeneity in right-ventricular heart failure inhibits excitation-contraction coupling and modulates arrhythmogenic dynamics.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.Frontiers in physiology · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The intracellular calcium handling system of cardiomyocytes is responsible for controlling excitation-contraction coupling (ECC) and has been linked to pro-arrhythmogenic cellular phenomena in conditions such as heart failure (HF). SERCA2a, responsible for intracellular uptake, is a primary regulator of calcium homeostasis, and remodelling of its function has been proposed as a causal factor underlying cellular and tissue dysfunction in disease. Whereas adaptations to the global (i.e. whole-cell) expression of SERCA2a have been previously investigated in the context of multiple diseases, the role of its spatial profile in the sub-cellular volume has yet to be elucidated. We present an approach to characterize the sub-cellular heterogeneity of SERCA2a and apply this approach to quantify adaptations to the length-scale of heterogeneity (the distance over which expression is correlated) associated with right-ventricular (RV)-HF. These characterizations informed simulations to predict the functional implications of this heterogeneity, and its remodelling in disease, on ECC, the dynamics of calcium-transient alternans and the emergence of spontaneous triggered activity. Image analysis reveals that RV-HF is associated with an increase in length-scale and its inter-cellular variability; simulations predict that this increase in length-scale can reduce ECC and critically modulate the vulnerability to both alternans and triggered activity. This article is part of the theme issue 'The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease'.
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