CaMKII cardiomyocyte model

• https://github.com/drgrandilab/Morotti-et-al-2014-Mouse-Ventricular-Model

• CaMKII model: “Mechanisms of Ca2+/calmodulin-dependent kinase II activation in single dendritic spines” (Chang et al., 2019, Nature Communications); Chang(2019)

• ROS activation model: Oxidized Calmodulin Kinase II Regulates Conduction Following Myocardial Infarction: A Computational Analysis (Christensen et al. 2009); Christensen(2019)

• Isoproterenol and CaMKII effects: A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII. (Moritti et al. 2014); Moritti(2014)

• Neonatal rat ventricular myocyte (NRVM) model: Model of Excitation-Contraction Coupling of Rat Neonatal Ventricular Myocytes (Korhonen et al. 2009); Korhonen(2009)

Adjusted from the original models¶

Beta-adrenergic system¶

The activities of PKACI, PKACII, PP1, and their downstream targets (SERCA, LCC, RyR, and NCX) are described by Hill functions, fitted to the activities in the original beta-adrenergic system in Moritti(2014) across a range of isoproterenol.

CaMKII system¶

• Association/dissociation rates of CaMKII and CaM-calcium (kf, kb) is fitted to Chang(2019) model across a range of cytosolic calcium concentrations.

• Autophosphorylation/dephosphorylation rates of CaMKII (kdp, kph) are adapted from Chang(2019) model.

• Oxidation/reduction rates of CaMKII (kox, krd) are adapted from Christensen(2019) model.

Neonatal rat ventricular cardiomyocyte (NRVM)¶

• Caffeine activation of RyR: increasing sensitivity to Sub-SR Ca instead of constant opening.

• Compartment corrections for SR Ca and Sub-SR Ca ODEs.

• Fast sodium channel gating variable recovery rates increased by 3 times to accommodate 2Hz and 3Hz pacing.