| Abstract | Intracellular free calcium signaling in cardiac myocytes has been studied extensively through both experiments and modeling. Of particular interest are the changes in bulk calcium concentration in the cytosol and endoplasmic reticulum and the dynamics of localized calcium elevations due to calcium release from clusters of calcium-regulated ion channels. This paper develops a hybrid whole cell model that accounts for both of these spatial scales of calcium signaling and examines the effect of stochastic calcium release (i.e. calcium sparks) on whole cell calcium homeostasis. When used to simulate experimental studies that examined the effects of tetracaine and flecainide on local and global calcium signaling, the model behaves consistently with experiments and supports the qualitative explanations of experimental results that appeared in Zima et al. Biophys. J. 94(5): 1867, 2008. [Supported by The College of William and Mary's NSF-funded Undergraduates in Biological and Mathematical Sciences (UBM) program and NSF Grant No. 0443843 to GDS.] |
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