Subcellular calcium dynamics in a whole-cell model of an atrial myocyte
In this study, we present an innovative mathematical modeling approach that allows detailed characterization of Ca(2+) movement within the three-dimensional volume of an atrial myocyte. Essential aspects of the model are the geometrically realistic representation of Ca(2+) release sites and physiolo...
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| Format: | Article |
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National Academy of Sciences
2012
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| Online Access: | https://eprints.nottingham.ac.uk/1761/ |
| _version_ | 1848790670439874560 |
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| author | Thul, Ruediger Coombes, Stephen Roderick, H. Llewelyn Bootman, Martin D. |
| author_facet | Thul, Ruediger Coombes, Stephen Roderick, H. Llewelyn Bootman, Martin D. |
| author_sort | Thul, Ruediger |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | In this study, we present an innovative mathematical modeling approach that allows detailed characterization of Ca(2+) movement within the three-dimensional volume of an atrial myocyte. Essential aspects of the model are the geometrically realistic representation of Ca(2+) release sites and physiological Ca(2+) flux parameters, coupled with a computationally inexpensive framework. By translating nonlinear Ca(2+) excitability into threshold dynamics, we avoid the computationally demanding time stepping of the partial differential equations that are often used to model Ca(2+) transport. Our approach successfully reproduces key features of atrial myocyte Ca(2+) signaling observed using confocal imaging. In particular, the model displays the centripetal Ca(2+) waves that occur within atrial myocytes during excitation-contraction coupling, and the effect of positive inotropic stimulation on the spatial profile of the Ca(2+) signals. Beyond this validation of the model, our simulation reveals unexpected observations about the spread of Ca(2+) within an atrial myocyte. In particular, the model describes the movement of Ca(2+) between ryanodine receptor clusters within a specific z disk of an atrial myocyte. Furthermore, we demonstrate that altering the strength of Ca(2+) release, ryanodine receptor refractoriness, the magnitude of initiating stimulus, or the introduction of stochastic Ca(2+) channel activity can cause the nucleation of proarrhythmic traveling Ca(2+) waves. The model provides clinically relevant insights into the initiation and propagation of subcellular Ca(2+) signals that are currently beyond the scope of imaging technology. |
| first_indexed | 2025-11-14T18:16:18Z |
| format | Article |
| id | nottingham-1761 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:16:18Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-17612020-05-04T20:22:56Z https://eprints.nottingham.ac.uk/1761/ Subcellular calcium dynamics in a whole-cell model of an atrial myocyte Thul, Ruediger Coombes, Stephen Roderick, H. Llewelyn Bootman, Martin D. In this study, we present an innovative mathematical modeling approach that allows detailed characterization of Ca(2+) movement within the three-dimensional volume of an atrial myocyte. Essential aspects of the model are the geometrically realistic representation of Ca(2+) release sites and physiological Ca(2+) flux parameters, coupled with a computationally inexpensive framework. By translating nonlinear Ca(2+) excitability into threshold dynamics, we avoid the computationally demanding time stepping of the partial differential equations that are often used to model Ca(2+) transport. Our approach successfully reproduces key features of atrial myocyte Ca(2+) signaling observed using confocal imaging. In particular, the model displays the centripetal Ca(2+) waves that occur within atrial myocytes during excitation-contraction coupling, and the effect of positive inotropic stimulation on the spatial profile of the Ca(2+) signals. Beyond this validation of the model, our simulation reveals unexpected observations about the spread of Ca(2+) within an atrial myocyte. In particular, the model describes the movement of Ca(2+) between ryanodine receptor clusters within a specific z disk of an atrial myocyte. Furthermore, we demonstrate that altering the strength of Ca(2+) release, ryanodine receptor refractoriness, the magnitude of initiating stimulus, or the introduction of stochastic Ca(2+) channel activity can cause the nucleation of proarrhythmic traveling Ca(2+) waves. The model provides clinically relevant insights into the initiation and propagation of subcellular Ca(2+) signals that are currently beyond the scope of imaging technology. National Academy of Sciences 2012 Article PeerReviewed Thul, Ruediger, Coombes, Stephen, Roderick, H. Llewelyn and Bootman, Martin D. (2012) Subcellular calcium dynamics in a whole-cell model of an atrial myocyte. Proceedings of the National Academy of Sciences, 109 (6). pp. 2150-2155. ISSN 1091-6490 http://www.pnas.org/content/109/6/2150 doi:10.1073/pnas.1115855109 doi:10.1073/pnas.1115855109 |
| spellingShingle | Thul, Ruediger Coombes, Stephen Roderick, H. Llewelyn Bootman, Martin D. Subcellular calcium dynamics in a whole-cell model of an atrial myocyte |
| title | Subcellular calcium dynamics in a whole-cell model of an atrial myocyte |
| title_full | Subcellular calcium dynamics in a whole-cell model of an atrial myocyte |
| title_fullStr | Subcellular calcium dynamics in a whole-cell model of an atrial myocyte |
| title_full_unstemmed | Subcellular calcium dynamics in a whole-cell model of an atrial myocyte |
| title_short | Subcellular calcium dynamics in a whole-cell model of an atrial myocyte |
| title_sort | subcellular calcium dynamics in a whole-cell model of an atrial myocyte |
| url | https://eprints.nottingham.ac.uk/1761/ https://eprints.nottingham.ac.uk/1761/ https://eprints.nottingham.ac.uk/1761/ |