Systems biology and multi-scale modeling of the heart

We are developing functionally integrated cell systems models of cardiac metabolism, signal transduction, excitation-contraction coupling, and myofilament interactions. These are then being incorporated into structurally integrated multi-scale models of cardiac electromechanical interactions that include tissue, organ and system scale properties. We describe new results with these models in which the effects of transmural heterogeneities in myocyte ionic currents and calcium handling on arrhythmia mechanisms and electromechanics are investigated.