Estimating the probabilities of rare arrhythmic events in multiscale computational models of cardiac cells and tissue
(a) Diagram of intracellular Ca2+ compartments and transport. At each release site at coordinates (i,j,k), Ca2+ is released via RyRs from the JSR into the dyadic subspace (SS) and diffuses into a submembrane (SM) compartment. Ca2+ diffuses between SM compartments of adjacent release sites in the 3D lattice, as depicted in panel (b). Ca2+ can also diffuse from the SM into a single cell-averaged cytosolic compartment and can be transported by the SR Ca2+ ATPase (SERCA pump) from the cytosolic compartment into a single network SR (NSR), which refills the JSR. (c) Illustration of the different spatial scales incorporated in the tissue model including (from left to right) the 48 stochastic RyRs in each of the 25,000 release sites of a single cell. Hundreds of cells are coupled via gap junction currents to form the fiber model.