diff --git a/docs/index.md b/docs/index.md index 6b2d9bb..0e35c18 100644 --- a/docs/index.md +++ b/docs/index.md @@ -5,21 +5,32 @@ --- -- CaMKII model: "Mechanisms of Ca2+/calmodulin-dependent kinase II activation in single dendritic spines" (Chang et al., 2019, Nature Communications); https://doi.org/10.1038/s41467-019-10694-z -- ROS activation model: Oxidized Calmodulin Kinase II Regulates Conduction Following Myocardial Infarction: A Computational Analysis (Christensen et al. 2009); https://doi.org/10.1371/journal.pcbi.1000583 -- 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); https://doi.org/10.1113/jphysiol.2013.266676 -- Neonatal rat ventricular myocyte model: Model of Excitation-Contraction Coupling of Rat Neonatal Ventricular Myocytes (Korhonen et al. 2009); https://pmc.ncbi.nlm.nih.gov/articles/PMC2716686/ +[Chang(2019)]: https://doi.org/10.1038/s41467-019-10694-z +[Christensen(2019)]: https://doi.org/10.1371/journal.pcbi.1000583 +[Moritti(2014)]: https://doi.org/10.1113/jphysiol.2013.266676 +[Korhonen(2009)]: https://pmc.ncbi.nlm.nih.gov/articles/PMC2716686/ + +- 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 -- Caffeine activation of RyR: increasing sensitivity to Sub-SR Ca instead of constant opening. -- Corrected compartment volumes for SR Ca and Sub-SR Ca ODEs. -- Added a simplified beta-adrenergic system with a steady-state algebraic representation. -- Fast sodium channel recovery rate increased by 3 times to accomodate 2Hz and 3Hz pacing. +### 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 -### Parameters adjusted +![Image](https://github.com/user-attachments/assets/37a18568-99f4-4b97-b410-f9052f6b58e7) -- kCaM4_on: 30 -> 15Hz / μM -- kCaM2C_on: 0.92 -> 0.5Hz / μM -- k_phosCaM: 30 -> 10Hz -- CmdnTotal: 50 -> 30μM +- Association/dissociation rates of CaMKII and CaM-calcium (kf, kb) is fitted to [Chang(2019)][] model across a range of cytosolic calcium. +- 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 accomodate 2Hz and 3Hz pacing.