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Subcellular calcium dynamics in a whole-cell model of an atrial myocyte

Thul, R�diger; Coombes, Stephen; Roderick, H. Llewelyn; Bootman, Martin D.


H. Llewelyn Roderick

Martin D. Bootman


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.


Thul, R., Coombes, S., Roderick, H. L., & Bootman, M. D. (2012). Subcellular calcium dynamics in a whole-cell model of an atrial myocyte. Proceedings of the National Academy of Sciences, 109(6), 2150-2155.

Journal Article Type Article
Publication Date Feb 7, 2012
Deposit Date Dec 21, 2012
Publicly Available Date Dec 21, 2012
Journal Proceedings of the National Academy of Sciences
Print ISSN 0027-8424
Electronic ISSN 1091-6490
Publisher National Academy of Sciences
Peer Reviewed Peer Reviewed
Volume 109
Issue 6
Pages 2150-2155
Public URL
Publisher URL
Additional Information Copyright: National Academy of Sciences


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