Figure 1.

(A) State diagram of the stochastic CaMKII activation model. Before the introduction of Ca²⁺/CaM, all CaMKII subunits are in the inactive form (state I). Activation occurs upon binding of Ca²⁺/CaM (state B), followed by autophosphorylation (state P) or 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 (asterisks) binding affinity for CaM (K_D) for the brain-specific α isoform (blue) and the cardiac-specific δ isoform (red) compared to experimental data (solid circles) of Gaertner et al. (16). (C) Simulated dose-response of CaMKII activation by H₂O₂ (red) compared to experimental data (black) of Erickson et al. (7). Simulations correspond to the experimental condition where [Ca²⁺] = 200 μM and [CaM] = 1 μM in the absence of ATP (to prevent autophosphorylation). To see this figure in color, go online.