Computational Modeling

Computational Modeling has allowed us to integrate a tremendous amount of biophysically detailed data into frameworks that both tests the limits of our quantitative mechanistic knowledge at more integrated levels and allows us to do novel in-silico experiments that help to refine critical new biologic experiments to fill our gaps in knowledge. Our 50+ modeling papers include electrodiffusion around mouths of ion channels, multiple-equilibria of complex ionic solutions (MaxChelator), dynamics of Ca buffering and fluxes in myocytes, ion channel gating models and several iterative integrated myocyte models incorporating all ion channels, Ca transport, Ca sparks (and analysis SparkMaster), Ca buffering, GPCR-kinase signaling and contractile properties. Our state-of-the-art models of rabbit, mouse, rat and human atrial & ventricular myocytes have been widely cited and used (we make these freely available to scientists everywhere). These models have provided unique insights into individual or complex system properties, identified quantitative gaps in our knowledge and have suggested novel hypotheses that help guide experiments.

 

1. Shannon TR, Wang F, Bers DM.  Regulation of cardiac sarcoplasmic reticulum Ca release by luminal [Ca] and altered gating assessed with a mathematical model.  Biophys J. 89:4096-4110, 2005.  614 Citations

2. Saucerman JJ, Bers DM.  Calmodulin mediates differential sensitivity of CaMKII and calcineurin to local Ca2+ in cardiac myocytes. Biophys J. 95:4597–4612, 2008. 

3. Grandi E, Pandit SV, Voigt N, Workman AJ, Dobrev D, Jalife J, Bers DM.  Human atrial action potential and Ca2+ model:  sinus rhythm and chronic atrial fibrillation. Circ Res 109:1055-1066, 2011.

4. Morotti S, Edwards AG, McCulloch AD, Bers DM, Grandi E.  A novel computational model of mouse myocyte electrophysiology to assess the synergy between Na+ loading and CaMKII. J Physiol. 592:1181-1197, 2014.

5. Negroni JA, Morotti S, Lascano EC, Gomes AV, Grandi E, Puglisi JL, Bers DM. β-adrenergic effects on cardiac myofilaments and contraction in an integrated rabbit ventricular myocyte model. J Mol Cell Cardiol. 81:162-175, 2015. 

6. Morotti S, Liu C, Hegyi B Ni H, Fogli Iseppe A, Wang L, Pritoni M, Ripplinger CM, Bers DM, Edwards AG, Grandi E. Quantitative cross-species translators of cardiac myocyte electrophysiology: model training, experimental validation, and applications. Sci Advances. Nov 19;7(47):eabg0927, 2021. doi: 10.1126/sciadv.abg0927