Subcellular calcium dynamics in a whole-cell model of an atrial myocyte
Proceedings of the National Academy of Sciences, 2012•National Acad Sciences
In this study, we present an innovative mathematical modeling approach that allows detailed
characterization of Ca2+ movement within the three-dimensional volume of an atrial
myocyte. Essential aspects of the model are the geometrically realistic representation of
Ca2+ release sites and physiological Ca2+ flux parameters, coupled with a computationally
inexpensive framework. By translating nonlinear Ca2+ excitability into threshold dynamics,
we avoid the computationally demanding time stepping of the partial differential equations …
characterization of Ca2+ movement within the three-dimensional volume of an atrial
myocyte. Essential aspects of the model are the geometrically realistic representation of
Ca2+ release sites and physiological Ca2+ flux parameters, coupled with a computationally
inexpensive framework. By translating nonlinear Ca2+ excitability into threshold dynamics,
we avoid the computationally demanding time stepping of the partial differential equations …
In this study, we present an innovative mathematical modeling approach that allows detailed characterization of Ca2+ movement within the three-dimensional volume of an atrial myocyte. Essential aspects of the model are the geometrically realistic representation of Ca2+ release sites and physiological Ca2+ flux parameters, coupled with a computationally inexpensive framework. By translating nonlinear Ca2+ excitability into threshold dynamics, we avoid the computationally demanding time stepping of the partial differential equations that are often used to model Ca2+ transport. Our approach successfully reproduces key features of atrial myocyte Ca2+ signaling observed using confocal imaging. In particular, the model displays the centripetal Ca2+ waves that occur within atrial myocytes during excitation–contraction coupling, and the effect of positive inotropic stimulation on the spatial profile of the Ca2+ signals. Beyond this validation of the model, our simulation reveals unexpected observations about the spread of Ca2+ within an atrial myocyte. In particular, the model describes the movement of Ca2+ between ryanodine receptor clusters within a specific z disk of an atrial myocyte. Furthermore, we demonstrate that altering the strength of Ca2+ release, ryanodine receptor refractoriness, the magnitude of initiating stimulus, or the introduction of stochastic Ca2+ channel activity can cause the nucleation of proarrhythmic traveling Ca2+ waves. The model provides clinically relevant insights into the initiation and propagation of subcellular Ca2+ signals that are currently beyond the scope of imaging technology.
National Acad Sciences