Synergy between intercellular communication and intracellular Ca2+ handling in arrhythmogenesis

Boileau, Etienne, George, Christopher H., Parthimos, Dimitris ORCID: https://orcid.org/0000-0003-3852-323X, Mitchell, Alice N., Aziz, Sabina and Nithiarasu, Perumal 2015. Synergy between intercellular communication and intracellular Ca2+ handling in arrhythmogenesis. Annals of Biomedical Engineering 43 , pp. 1614-1625. 10.1007/s10439-014-1243-x

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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 Ca 2+ Ca2+ 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 Ca 2+ Ca2+ dynamics. Theoretical predictions successfully reproduced experimental findings and provide novel insights on the action of two pharmacological agents (ionomycin and verapamil) that modulate Ca 2+ Ca2+ 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 intracellular Ca 2+ Ca2+ 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 Ca 2+ Ca2+ perturbations in cardiac tissue in situ.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Additional Information:	PDF uploaded in accordance with publisher's policies at http://www.sherpa.ac.uk/romeo/issn/0090-6964/ (accessed 16.6.16).
Publisher:	Springer Verlag
ISSN:	0090-6964
Date of First Compliant Deposit:	16 June 2016
Date of Acceptance:	29 December 2014
Last Modified:	10 Nov 2023 13:40
URI:	https://orca.cardiff.ac.uk/id/eprint/91868

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