Evaluation and Preliminary Integration of the Most Recent Human Ventricular Action Potential Models

Lorenzo Gorgolini, Chiara Bartolucci, Stefano Severi
University of Bologna


Computational models of ventricular action potentials are a very important tool in the study of cardiac electrophysiology and can provide important data for the study of arrhythmias and the underlying mechanisms at the level of ionic currents and single ventricular myocyte action potential (AP). However, there is currently no model capable of reproducing all the experimental results. This work aims to answer the question: is it possible to integrate the innovations introduced by the two most recent models of ventricular AP in a new model, keeping unchanged the positive results that each model has shown? This new model follows the general ORd structure and starting from the analysis of the differences between the two models (Tomek et al. and Bartolucci et al); we decided to introduce the ICaL formulation adopted from the BPS model, a modification to the driving force taken from the ToRORd which led to the development of a new formulation for the ICaL activation curve. Besides, we decided to keep the sarcoplasmic reticulum as a single compartment and the IKr formulation used in BPS while we have changed IK1 formulation, inserted calcium-sensitive chloride current I(Ca)Cl, and background chloride current IClb like the one used in ToRORd. The new model was tested with some of the protocols used for the BPS and ToRORd models and it was found that the new model can reproduce the negative dependence of the APD on the extracellular calcium. In addition, there is a notable improvement in the results of the activation protocol: the I-V curve obtained with the new model is very close to the experimental data. Unlike the ToRORd the new model fails to reproduce the negative inotropic effect of sodium blockade but at least we do not have a strong pro-inotropic effect like in the ORd model.