Fig. 8.

Schematic of the underlying mechanism of DADs. An increase in Ca_Tot within the cell increases the level of Ca²⁺ within each compartment. The increase in the dyadic subspace leads to a higher open probability of RyRs, increasing the spark rate, which, at some point, initiates a concerted opening of RyRs throughout the cell (a release). (As shown in Fig. 3, the modulation by Ca_SR content is influential but not essential.) The intracellular (Ca²⁺ subsystem) oscillations are maintained by the fast and slow time constants of diffusion, uptake, and release; in some models, NCX is necessary for the oscillations, but parameter changes in the model can make it redundant. The intracellular Ca²⁺ oscillations are then translated either via NCX, the Ca²⁺-activated Cl⁻ channel, or nonspecific Ca²⁺-activated current to changes in voltage, which can eventually trigger a complete AP (see Fig. 1). I_SERCA, SERCA current; NSR and JSR, network and junctional SR; I_di, diffusion current; I_NaCa, Na⁺/Ca²⁺ exchange current.