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Calcium Cycling Disturbances And Arrhythmogenesis, Namit Gaur

McKelvey School of Engineering Theses & Dissertations

In this work, a detailed multiscale computational model of Ca cycling and action potential in a ventricular myocyte is developed and used to study mechanisms of arrhythmias associated with mutations in the ryanodine receptor (RyR). The multiscale ventricular myocyte model reproduces experimentally observed Ca dynamics both at the local dyadic scale and at the global whole-cell scale, while also simulating the action potential (AP) shaped by membrane ionic currents. The model represents stochastic activation of L-type Ca channels (LCCs) and RyRs in the dyads and simulates random generation of Ca sparks both during excitation-contraction coupling (ECC) and during diastole. The …