Fig. 3.

Elucidating the necessary underlying mechanism for DADs in different mathematical models. The top and middle rows show the output of the full model (Shannon04), whereas the bottom row denotes the Ca²⁺ content of the SR in the reduced model. Na⁺ and thus Ca²⁺ overload was established by setting the initial intracellular Na⁺ to 35 mM. A: original model. B: model without the modulation of sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) by SR content. C: model without modulation of RyRs by SR content. D: model without modulation of RyRs by the dyadic subspace. It was apparent that only the modulation of RyR by dyadic subspace Ca²⁺ (Ca_Dyad) is essential for DADs and Ca²⁺ oscillations, as its removal led to diminishing oscillations. In C, the x-axis is shifted as it took a longer time until the DADs appearred after the switch to the slower pacing frequency.