Computational modeling and numerical methods for spatiotemporal calcium cycling in ventricular myocytes

Intracellular calcium (Ca) cycling dynamics in cardiac myocytes is regulated by a complex network of spatially distributed organelles, such as sarcoplasmic reticulum (SR), mitochondria, and myofibrils. In this study, we present a mathematical model of intracellular Ca cycling and numerical and computational methods for computer simulations. The model consists of a coupled Ca release unit (CRU) network, which includes a SR domain and a myoplasm domain. Each CRU contains 10 Ltype Ca channels and 100 ryanodine receptor channels, with individual channels simulated stochastically using a variant of Gillespie's method, modified here to handle time-dependent transition rates. Both the SR domain and the myoplasm domain in each CRU are modeled by 5 x 5 x 5 voxels to maintain proper Ca diffusion. Advanced numerical algorithms implemented on graphical processing units were used for fast computational simulations. For a myocyte containing 100 x 20 x 10 CRUs, a 1-s heart time simulation takes about 10 min of machine time on a single NVIDIA Tesla C2050. Examples of simulated Ca cycling dynamics, such as Ca sparks, Ca waves, and Ca alternans, are shown.