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Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis / Etienne Boileau, Christopher George, Dimitris Parthimos, Alice N. Mitchell, Sabina Aziz, Perumal Nithiarasu

Annals of Biomedical Engineering, Volume: 43, Issue: 7, Pages: 1614 - 1625

Swansea University Authors: Christopher George, Perumal Nithiarasu

Abstract

Calcium is the primary signalling component of excitation-contraction coupling, the process linking electrical excitability of cardiac muscle cells to coordinated contraction of the heart. Understanding Ca2þ handling processes at the cellular level and the role of intercellular communication in the...

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Published in: Annals of Biomedical Engineering
ISSN: 0090-6964 1573-9686
Published: 2015
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa21238
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Abstract: Calcium is the primary signalling component of excitation-contraction coupling, the process linking electrical excitability of cardiac muscle cells to coordinated contraction of the heart. Understanding Ca2þ handling processes at the cellular level and the role of intercellular communication in the emergence of multicellular synchronization are key aspects in the study of arrhythmias. To probe these mechanisms, we have simulated cellular interactions on large scale arrays that mimic cardiac tissue, and where individual cells are represented by a mathematical model of intracellular Ca2þ dynamics. Theoretical predictions successfully reproduced experimental findings and provide novel insights on the action of two pharmacological agents (ionomycin and verapamil) that modulate Ca2þ signalling pathways via distinct mechanisms. Computational results have demonstrated how transitions between local synchronisation events and large scale wave formation are affected by these agents. Entrainment phenomena are shown to be linked to both ntracellular Ca2þ and coupling-specific dynamics in a synergistic manner. The intrinsic variability of the cellular matrix is also shown to affect emergent patterns of rhythmicity, providing insights into the origins of arrhythmogenic Ca2þ perturbations in cardiac tissue in situ.
Keywords: Membrane potential, Intra cellular oscillator, Coupling, Synchronisation, Complex dynamical system, Emergence.
College: College of Engineering
Issue: 7
Start Page: 1614
End Page: 1625