Oxidized Calmodulin Kinase II Regulates Conduction Following Myocardial Infarction: A Computational Analysis
Figure 2
Mathematical model of CaMKII activity.
(A) State diagram for CaMKII including activation by Ca2+/CaM (B), oxidation (Ox), and autophosphorylation (P). Rate constants are provided in supplementary information (Text S1 and Table S3). (B) Simulated dose-dependent activation of CaMKII by H2O2 compared to experiment [12]. Ca2+/CaM = 1 µM and autophosphorylation rate = 0 in simulations corresponding to the following experimental conditions: 200 µM Ca2+, 1 µM CaM in the absence of ATP (to prevent autophosphorylation). Simulated CaM dependence of (C) CaMKII activity and (D) autophosphorylation compared to experiment [50]. Saturating conditions for Ca2+ (Ca2+ = 0.5 mM) are used in experiment and simulation to allow for control of [Ca2+/CaM] by varying [CaM]. (E) Simulated levels of CaMKII oxidation and autophosphorylation in the BZ model for different levels of oxidative stress (model paced to steady-state at cycle length of 500 ms).