ArticlePloS one2013
Formation of spatially discordant alternans due to fluctuations and diffusion of calcium.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Multiscale stochastic modeling for calcium dynamics in cardiac electrophysiology: assessing whole-cell model reliability under phosphorylation and LCC downregulation.Frontiers in network physiology · 2026Article
- Dynamical effects of mechano-chemo-transduction on cardiac alternans.Biophysical journal · 2025Article
- Ephaptic Coupling as a Resolution to the Paradox of Action Potential Wave Speed and Discordant Alternans Spatial Scales in the Heart.Physical review letters · 2023Article
- Role of ephaptic coupling in discordant alternans domain sizes and action potential propagation in the heart.Physical review. E · 2023Article
- CardIAP: calcium transients confocal image analysis tool.Frontiers in bioinformatics · 2023Article
- Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges.Biomolecules · 2022Review
- Biological noise is a key determinant of the reproducibility and adaptability of cardiac pacemaking and EC coupling.The Journal of general physiology · 2022Review
- Synchronization of spatially discordant voltage and calcium alternans in cardiac tissue.Physical review. E · 2022Article
- Voltage-mediated mechanism for calcium wave synchronization and arrhythmogenesis in atrial tissue.Biophysical journal · 2022Article
- Multi-Scale Computational Modeling of Spatial Calcium Handling From Nanodomain to Whole-Heart: Overview and Perspectives.Frontiers in physiology · 2022Review
- Cardiac Alternans Occurs through the Synergy of Voltage- and Calcium-Dependent Mechanisms.Membranes · 2021Article
- Electrophysiological Mechanisms Underlying T-Wave Alternans and Their Role in Arrhythmogenesis.Frontiers in physiology · 2021Review
- Stability of spatially discordant repolarization alternans in cardiac tissue.Chaos (Woodbury, N.Y.) · 2020Article
- Dual regulation by subcellular calcium heterogeneity and heart rate variability on cardiac electromechanical dynamics.Chaos (Woodbury, N.Y.) · 2020Article
- Sensitivity of a data-assimilation system for reconstructing three-dimensional cardiac electrical dynamics.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2020Article
- Spatially Discordant Repolarization Alternans in the Absence of Conduction Velocity Restitution.Biophysical journal · 2020Article
- A Computational Pipeline to Predict Cardiotoxicity: From the Atom to the Rhythm.Circulation research · 2020Article
- Stochastic coupled map model of subcellular calcium cycling in cardiac cells.Chaos (Woodbury, N.Y.) · 2019Article
- β-Adrenergic Receptor Stimulation and Alternans in the Border Zone of a Healed Infarct: AnFrontiers in physiology · 2019Article
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3 authors.
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Abstract
Spatially discordant alternans (SDA) of action potential duration (APD) is a phenomenon where different regions of cardiac tissue exhibit an alternating sequence of APD that are out-of-phase. SDA is arrhythmogenic since it can induce spatial heterogeneity of refractoriness, which can cause wavebreak and reentry. However, the underlying mechanisms for the formation of SDA are not completely understood. In this paper, we present a novel mechanism for the formation of SDA in the case where the cellular instability leading to alternans is caused by intracellular calcium (Ca) cycling, and where Ca transient and APD alternans are electromechanically concordant. In particular, we show that SDA is formed when rapidly paced cardiac tissue develops alternans over many beats due to Ca accumulation in the sarcoplasmic reticulum (SR). The mechanism presented here relies on the observation that Ca cycling fluctuations dictate Ca alternans phase since the amplitude of Ca alternans is small during the early stages of pacing. Thus, different regions of a cardiac myocyte will typically develop Ca alternans which are opposite in phase at the early stages of pacing. These subcellular patterns then gradually coarsen due to interactions with membrane voltage to form steady state SDA of voltage and Ca on the tissue scale. This mechanism for SDA is distinct from well-known mechanisms that rely on conduction velocity restitution, and a Turing-like mechanism known to apply only in the case where APD and Ca alternans are electromechanically discordant. Furthermore, we argue that this mechanism is robust, and is likely to underlie a wide range of experimentally observed patterns of SDA.
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