Arrhythmia mechanisms and spontaneous calcium release: Bi-directional coupling between re-entrant and focal excitation

PLoS Computational Biology
Michael A Colman

Abstract

Spontaneous sub-cellular calcium release events (SCRE) are conjectured to promote rapid arrhythmias associated with conditions such as heart failure and atrial fibrillation: they can underlie the emergence of spontaneous action potentials in single cells which can lead to arrhythmogenic triggers in tissue. The multi-scale mechanisms of the development of SCRE into arrhythmia triggers, and their dynamic interaction with the tissue substrate, remain elusive; rigorous and simultaneous study of dynamics from the nanometre to the centimetre scale is a major challenge. The aim of this study was to develop a computational approach to overcome this challenge and study potential bi-directional coupling between sub-cellular and tissue-scale arrhythmia phenomena. A framework comprising a hierarchy of computational models was developed, which includes detailed single-cell models describing spatio-temporal calcium dynamics in 3D, efficient non-spatial cell models, and both idealised and realistic tissue models. A phenomenological approach was implemented to reproduce SCRE morphology and variability in the efficient cell models, comprising the definition of analytical Spontaneous Release Functions (SRF) whose parameters may be randomly sampl...Continue Reading

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Citations

Aug 31, 2020·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Tang ZhangHao Liu
Sep 25, 2020·PLoS Computational Biology·Miquel MarchenaEnrique Alvarez-Lacalle
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Feb 23, 2021·Biophysical Journal·D'Artagnan Greene, Yohannes Shiferaw
Jun 3, 2021·Biomedicines·Magali SeguretJean-Sébastien Hulot
Jul 25, 2021·International Journal of Molecular Sciences·Jieyun BaiJichao Zhao
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