Abstract Summary/Description
A Compartmentalized Mathematical Model of Hypertrophic Mouse Ventricular Myocytes Dilmini Warnakulasooriya1 and Vladimir E. Bondarenko1,2 1Department of Mathematics and Statistics and 2Neuroscience Institute, Georgia State University, Atlanta, GA, USA Compensated cardiac hypertrophy is considered as an adaptive response of the myocytes to increased workload and develops at early stages of heart failure. Experimentally, cardiac hypertrophy is induced by the procedure called transverse aortic constriction (TAC) during the first week after surgery. It is believed that during the early stage of hypertrophy the heart increases its function without adverse effects. To investigate cardiac hypertrophy, we developed a new comprehensive compartmentalized mathematical model of hypertrophic mouse ventricular myocytes that described the cell geometry, cardiac action potentials, [Ca2+]i transients, and β1- and β2-adrenergic signaling systems. Simulation results obtained with the hypertrophic cell model were compared to those from the normal ventricular myocyte model. Our model simulations revealed the prolongation of the action potential, increased [Ca2+]i transients, lower adenylyl cyclase activity, and generation of pro-arrhythmic events called early afterdepolarizations (EADs) in hypertrophic myocytes as compared to control myocytes. We also explored the mechanisms of EAD for slow stimulation rates (< 1 Hz) upon application of 1 μM of β-adrenergic agonist isoproterenol, which demonstrated a synergistic effect of the late Na+ current INaL, the T-type Ca2+ current ICaT, the L-type Ca2+ current ICaL, and the slow component of the fast Na+ current INa in generation of EADs.
