Figure 2.

(A) State diagram of the stochastic CaMKII activation model of Foteinou et al. (2013). Prior to the introduction of Ca²⁺/CaM, all of the CaMKII subunits are in the inactive form (state I). Activation occurs upon binding of Ca²⁺/CaM (state B), autophosphorylation (state P), and oxidation (state Ox_B). Autonomous active states (Ca²⁺/CaM-unbound) can be either autophosphorylated (state A) or oxidized (state Ox_A). The model also includes an active state that is both oxidized and phosphorylated (state Ox_P). (B) Simulated steady state APs under control conditions (0 μM H₂O₂). (C) Simulated APs, some of which exhibit EADs, under conditions of elevated oxidant stress (200 μM H₂O₂). Simulated APs are from a 2 s PCL pacing protocol (ensemble of 12500 calcium release units). For each condition, results for 10 consecutive APs following an initial 10 s of pacing are shown.