Figure 1.

The modules of the model and their interaction. The mathematical model comprises a set of partial differential equations (PDEs) for the bulk concentrations of cytosolic and sarcoplasmic free Ca²⁺, cytosolic and sarcoplasmic mobile buffers and a cytosolic stationary buffer. The N_c Ca²⁺ release units (CRUs) are simulated all individually and are source terms in the bulk concentration dynamics PDEs. The state dynamics of each of their LC- or RyR-channels is a continuous time Markov chain. The concentration profile in the dyadic space is modeled in spatial detail with a quasistationary approximation, the dynamics of the concentrations of free Ca²⁺ and buffer in the jSR are determined by release into the cleft and refilling from the network SR (nSR). The electrophysiology model has been developed by Mahajan et al. (2008a). The LCC current in the CRUs and the Na⁺/Ca²⁺-exchanger flux couple the membrane potential dynamics directly to the concentration dynamics.