Computational Analysis of Extracellular Calcium Effects on an Improved Human Ventricular Action Potential Model

A decrease in extracellular calcium concentration ([Ca2+]o) prolongs the action potential (AP) in ventricular cardiomyocytes, and viceversa. Although this phenomenon can be relevant to arrhythmogenesis in clinical settings, it is not included in most of the commonly used computational models of ventricular AP. Therefore, the aim of this study has been to improve a recently published human ventricular model (O’Hara-Rudy, 2011), in order to reproduce the inverse relationship between [Ca2+]o and AP duration (APD). The original L-type Calcium current (ICaL) formulation has been replaced by a minimal Markov chain, developed on purpose. Some minor modifications were also implemented to preserve the physiological behavior of the whole cell and to maintain consistency with the experimental data reported in the original paper. Thus, the modified model can be used as a framework to explore the impact of [Ca2+]o imbalances on the myocyte electrical activity. Further modifications are foreseen to improve model behavior in a larger variety of contexts.