Simulation of excitation contraction coupling in ventricular cardiac myocytes
Final Report Abstract
The major aim of the project was to establish simulations of excitation contraction coupling (ECC) in ventricular cardiac myocytes, during which 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). This has been realized. The clefts’ ion channels have been modeled in molecular state detail as stochastic processes. Membrane potential dynamics is species specific. We have developed 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 have developed algorithms allowing for the use of both but the complete space-time adaptive grids are not fully functional, yet (see below). Higher order linearly implicit Runge-Kutta methods are applied to meet the time step management challenges. The size of the problem requires high performance computing on many CPUs. We have developed the corresponding load balancing methods. Simulations are running typically on 4 nodes with 16 cores each on the MDC’s HPC cluster. The group Falcke in Berlin and the group of S. Luther, MPI DS Göttingen, are using the simulation for biological research, now.
Publications
- A multiscale computational model of spatially resolved calcium cycling in cardiac myocytes: from detailed cleft dynamics to the whole cell concentration profiles, Frontiers in Physiology, 6(255) (2015), pp. 1664-042X
J. Vierheller, W. Neubert, M. Falcke, S. H. Gilbert, N. Chamakuri
(See online at https://doi.org/10.3389/fphys.2015.00255) - Multiscale modeling of calcium cycling in cardiac myocytes. Multiscale Modeling & Simulation, 16(3) (2018), pp. 1115 –1145
Ch. Nagaiah and W. Neubert and S. Gilbert and J. Vierheller and G. Warnecke and M. Falcke
