Simulation of excitation contraction coupling in ventricular cardiac myocytes

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Arrhythmias and fibrillation are among the prime causes of cardiac death. They may arise from alternans and other arrhythmogenic processes on cell level. Ca2+ dynamics are involved in a variety of them. The project will investigate cellular arrhythmogenic processes, which are known in part but far from completely understood especially in their interaction, by simulating excitation contraction coupling (ECC) in ventricular cardiac myocytes. Membrane excitation is translated into a Ca2+ signal in thousands of tiny dyadic clefts inside the cell. The problem's large range of space and time scales requires a multi-scale technique, which describes the concentration gradients in the clefts by quasi-static Green's functions, and simulates the bulk reaction-diffusion processes with finite element methods (FEMs). The cleft's ion channels will be modeled in molecular state detail as stochastic processes. Membrane potential dynamics will be cell type and species specific. We will develop hybrid stochastic-deterministic time step management specified to the problem. The range of space and time scales in the bulk processes requires spatial and temporal adaptivity of the FEM. We will develop algorithms allowing for the use of both. Higher order linearly implicit Runge-Kutta methods will be applied to meet the time step management challenges. The size of the problem requires high performance computing on many CPUs involving appropriately developed load balancing methods.