Intracellular Ca2+ nonlinear wave behaviours in a three dimensional ventricular cell model

Intracellular Ca2+ activity regulates a wide range of cellular biochemical processes; in muscle cells, it links membrane excitation to contraction. Ca2+ dynamics includes both synchronous oscillations, and nonlinear wave phenomena, both arising from the superposition of spatially localised stochastic events, such as Ca2+ sparks. We incorporated individualised cell geometry reconstructed from confocal microscopy with realistic spatial distribution of RyR clusters into the three dimensional ventricular cell model, and reproduced complex spatio-temporal intracellular wave patterns from Ca2+ sparks. We also introduced a detailed nuclear Ca2+ handing model to simulate prolonged nuclear Ca2+ transient, and study the effects of cytosolic-nuclear coupling on intracellular Ca2+ dynamics. The model provides a computational platform to study intracellular Ca2+ with the ability to interact with experimental measurements of subcellular structures, and can be modified for other cell types.