FIGURE 5.

Foundational models for idealized geometric modeling of cardiac ECC. (A) Two important early dyadic structure models involving stochastic RyR dynamics were provided by Sobie’s sticky cluster (Sobie et al., 2002) (A), and the 4-couplon model of Greenstein and Winslow (2002) (B). These two average dyadic models were each then extended to simulate whole-cell ECC by instantiating the 12,500–20,000 stochastically operating CRUs in the average ventricular myocyte Williams et al. (2011) and Wescott et al. (2016) (C). Implemented models that solved stochastic RyR dynamics across these many identical sticky-cluster-derived CRUs, whereas Hinch et al. (2004) and Hinch (2004) performed a clever timescale decomposition to markedly reduce the scale of the problem (D). Both families of model have been successful in replicating and/or interrogating a number of important macroscopic properties of ECC. However, neither is readily capable of assessing the impact of local RyR dispersion, and they do not implement known heterogeneities in CRU structure and function (see Section 2). Copyright permission to reproduce the figures.