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On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach

Alberto Coccarelli Orcid Logo, Sanjay Pant Orcid Logo

Computers in Biology and Medicine, Volume: 164

Swansea University Authors: Alberto Coccarelli Orcid Logo, Sanjay Pant Orcid Logo

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DOI (Published version): 10.1016/j.compbiomed.2023.107111

Abstract

Agonist-induced Ca2+ signalling is essential for the regulation of many vital functions in endothelial cells (ECs). A broad range of stimuli elevate the cytosolic Ca2＋ concentration by promoting a pathway mediated by inositol 1,4,5 trisphosphate (IP) which causes Ca2＋ release from intracellular stor...

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Published in: Computers in Biology and Medicine
ISSN: 0010-4825 1879-0534
Published: Elsevier 2023
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URI: https://cronfa.swan.ac.uk/Record/cronfa63619
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spelling v2 63619 2023-06-12 On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach 06fd3332e5eb3cf4bb4e75a24f49149d 0000-0003-1511-9015 Alberto Coccarelli Alberto Coccarelli true false 43b388e955511a9d1b86b863c2018a9f 0000-0002-2081-308X Sanjay Pant Sanjay Pant true false 2023-06-12 MECH Agonist-induced Ca2+ signalling is essential for the regulation of many vital functions in endothelial cells (ECs). A broad range of stimuli elevate the cytosolic Ca2＋ concentration by promoting a pathway mediated by inositol 1,4,5 trisphosphate (IP) which causes Ca2＋ release from intracellular stores. Despite its importance, there are very few studies focusing on the quantification of such dynamics in the vascular endothelium. Here, by using data from isolated ECs, we established a minimalistic modeling framework able to quantitatively capture the main features (averaged over a cell population) of the cytosolic Ca2＋ response to different IP stimulation levels. A suitable description of Ca2＋-regulatory function of inositol 1,4,5 trisphosphate receptors (IPRs) and corresponding parameter space are identified by comparing the different model variants against experimental mean population data. The same approach is used to numerically assess the relevance of cytosolic Ca2＋ buffering, as well as Ca2＋ store IP-sensitivity in the overall cell dynamics. The variability in the dynamics’ features observed across the population can be explained (at least in part) through variation of certain model parameters (such as buffering capacity or Ca2＋ store sensitivity to IP). The results, in terms of experimental fitting and validation, support the proposed minimalistic model as a reference framework for the quantification of the EC Ca2＋ dynamics induced by IPRs activation. Journal Article Computers in Biology and Medicine 164 Elsevier 0010-4825 1879-0534 Ca2+ dynamics, Endothelial cells, Inositol trisphosphate-sensitive store receptors activation, Vascular function, Quantitative biology, Data-driven modeling 1 9 2023 2023-09-01 10.1016/j.compbiomed.2023.107111 COLLEGE NANME Mechanical Engineering COLLEGE CODE MECH Swansea University SU Library paid the OA fee (TA Institutional Deal) Swansea University 2023-09-07T16:43:49.2454991 2023-06-12T09:55:58.1945745 Faculty of Science and Engineering School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Mechanical Engineering Alberto Coccarelli 0000-0003-1511-9015 1 Sanjay Pant 0000-0002-2081-308X 2 63619__28429__f3a6af638d46458fa8c51cca4345fc75.pdf 63619 VOR.pdf 2023-09-04T10:51:13.1711149 Output 3431420 application/pdf Version of Record true Crown Copyright © 2023 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). true eng http://creativecommons.org/licenses/by/4.0/
title On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach
spellingShingle On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach
Alberto Coccarelli
Sanjay Pant
title_short On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach
title_full On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach
title_fullStr On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach
title_full_unstemmed On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach
title_sort On the Ca2＋ elevation in vascular endothelial cells due to inositol trisphosphate-sensitive store receptors activation: A data-driven modeling approach
author_id_str_mv 06fd3332e5eb3cf4bb4e75a24f49149d
43b388e955511a9d1b86b863c2018a9f
author_id_fullname_str_mv 06fd3332e5eb3cf4bb4e75a24f49149d_***_Alberto Coccarelli
43b388e955511a9d1b86b863c2018a9f_***_Sanjay Pant
author Alberto Coccarelli
Sanjay Pant
author2 Alberto Coccarelli
Sanjay Pant
format Journal article
container_title Computers in Biology and Medicine
container_volume 164
publishDate 2023
institution Swansea University
issn 0010-4825
1879-0534
doi_str_mv 10.1016/j.compbiomed.2023.107111
publisher Elsevier
college_str Faculty of Science and Engineering
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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 - Mechanical Engineering{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Aerospace, Civil, Electrical, General and Mechanical Engineering - Mechanical Engineering
document_store_str 1
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description Agonist-induced Ca2+ signalling is essential for the regulation of many vital functions in endothelial cells (ECs). A broad range of stimuli elevate the cytosolic Ca2＋ concentration by promoting a pathway mediated by inositol 1,4,5 trisphosphate (IP) which causes Ca2＋ release from intracellular stores. Despite its importance, there are very few studies focusing on the quantification of such dynamics in the vascular endothelium. Here, by using data from isolated ECs, we established a minimalistic modeling framework able to quantitatively capture the main features (averaged over a cell population) of the cytosolic Ca2＋ response to different IP stimulation levels. A suitable description of Ca2＋-regulatory function of inositol 1,4,5 trisphosphate receptors (IPRs) and corresponding parameter space are identified by comparing the different model variants against experimental mean population data. The same approach is used to numerically assess the relevance of cytosolic Ca2＋ buffering, as well as Ca2＋ store IP-sensitivity in the overall cell dynamics. The variability in the dynamics’ features observed across the population can be explained (at least in part) through variation of certain model parameters (such as buffering capacity or Ca2＋ store sensitivity to IP). The results, in terms of experimental fitting and validation, support the proposed minimalistic model as a reference framework for the quantification of the EC Ca2＋ dynamics induced by IPRs activation.
published_date 2023-09-01T16:43:50Z
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