Abstract: Ventricular fibrillation (VF) is due to re-entrant waves that can be created as a result of dynamic wave instability. Ventricular action potential (VAP) models have been used to understand the mechanisms underlying dynamic wavebreak. However, currently there exists no model of ventricular AP that replicates voltage dynamics of cardiac AP and intracellular calcium (Ca) cycling at heart rates relevant to ventricular tachyarrhythmias. Additionally, no model incorporates a physiologic Markov formulation L-type Ca current (ICa, _L), which is an important modulator of dynamic wave stability. Blocking the amplitude of ICa,_L can prevent wavebreak, however it also suppresses contractility. The essential aims of this thesis are to- (1) develop a rabbit VAP model that incorporates a physiologic Markov ICa,_L formulation and reproduces experimentally observed dynamics of rabbit myocytes paced at rapid stimulation rates, (2) Use the new model to predict therapeutic strategies of preventing VF by altering ICa,_L kinetics while preserving contractility. We develop a new VAP model by including the ICa,_L and Ca cycling formulations based on experimental data obtained in rabbit ventricular myocytes at 37°C. The model replicates experimentally-observed cardiac AP dynamics at rapid heart rates. Computer simulations using our model predict that blocking ICa,_L inactivation while maintaining a normal APD, flattens APD restitution slope, prevents APD and Ca transient alternans, yet maintains a normal Ca transient amplitude. Experimentally, we confirm this strategy by utilizing a gene therapy approach of overexpressing a mutant Ca-insensitive calmodulin in rabbit ventricular myocytes. In summary, the studies in this thesis work establish a new VAP model that reliably reproduces the dynamical properties at rapid heart rates relevant to ventricular tachyarrhythmias and provide proof-of concept for a novel experimental strategies of modifying ICa,_L to prevent VF.