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Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis

Etienne Boileau, Christopher George Orcid Logo, Dimitris Parthimos, Alice N. Mitchell, Sabina Aziz, Perumal Nithiarasu Orcid Logo

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

Swansea University Authors: Christopher George Orcid Logo, Perumal Nithiarasu Orcid Logo

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DOI (Published version): 10.1007/s10439-014-1243-x

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
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URI: https://cronfa.swan.ac.uk/Record/cronfa21238
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spelling 2021-01-07T13:40:31.8723787 v2 21238 2015-05-08 Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis a2e211f7bd379c81e9c393637803a0a0 0000-0001-9852-1135 Christopher George Christopher George true false 3b28bf59358fc2b9bd9a46897dbfc92d 0000-0002-4901-2980 Perumal Nithiarasu Perumal Nithiarasu true false 2015-05-08 BMS 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. Journal Article Annals of Biomedical Engineering 43 7 1614 1625 0090-6964 1573-9686 Membrane potential, Intra cellular oscillator, Coupling, Synchronisation, Complex dynamical system, Emergence. 31 7 2015 2015-07-31 10.1007/s10439-014-1243-x http://link.springer.com/article/10.1007/s10439-014-1243-x COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2021-01-07T13:40:31.8723787 2015-05-08T09:23:37.1647399 Faculty of Science and Engineering School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Civil Engineering Etienne Boileau 1 Christopher George 0000-0001-9852-1135 2 Dimitris Parthimos 3 Alice N. Mitchell 4 Sabina Aziz 5 Perumal Nithiarasu 0000-0002-4901-2980 6 0021238-21072016105840.pdf boileau15av2.pdf 2016-07-21T10:58:40.5300000 Output 1732585 application/pdf Accepted Manuscript true 2016-07-21T00:00:00.0000000 false
title Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis
spellingShingle Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis
Christopher George
Perumal Nithiarasu
title_short Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis
title_full Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis
title_fullStr Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis
title_full_unstemmed Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis
title_sort Synergy Between Intercellular Communication and Intracellular Ca2+ Handling in Arrhythmogenesis
author_id_str_mv a2e211f7bd379c81e9c393637803a0a0
3b28bf59358fc2b9bd9a46897dbfc92d
author_id_fullname_str_mv a2e211f7bd379c81e9c393637803a0a0_***_Christopher George
3b28bf59358fc2b9bd9a46897dbfc92d_***_Perumal Nithiarasu
author Christopher George
Perumal Nithiarasu
author2 Etienne Boileau
Christopher George
Dimitris Parthimos
Alice N. Mitchell
Sabina Aziz
Perumal Nithiarasu
format Journal article
container_title Annals of Biomedical Engineering
container_volume 43
container_issue 7
container_start_page 1614
publishDate 2015
institution Swansea University
issn 0090-6964
1573-9686
doi_str_mv 10.1007/s10439-014-1243-x
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Civil Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Civil Engineering
url http://link.springer.com/article/10.1007/s10439-014-1243-x
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description 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.
published_date 2015-07-31T03:24:16Z
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