ToR-ORd-dynCl: an update of the ToR-ORd model of human ventricular cardiomyocyte with dynamic intracellular chloride

Abstract

Recently, our group published a new model of human ventricular cardiomyocyte named ToR-ORd (Tomek et al., 2019). Its development, calibration, and validation, were performed using a broad range of human experimental data and brought general insights into modelling of ionic channels. Model calibration ensured the reproduction of key physiological cellular features, with independent multiscale validation demonstrating a correct response to channel blocking drugs and pathophysiological remodelling. However, for very long simulations (several hours rather than minutes), the ToR-ORd simulations display a drift in its behaviour, caused by modelling chloride concentrations as constant values. This may be a limitation for simulations considering extremely long protocols, or for studies on model stability. To remedy this, we present here an updated version, termed ToR-ORd-dynCl, with dynamic representation of intracellular chloride. This model behaves very similarly to the original ToR-ORd, but with stable properties over long simulations and only a small increase in model complexity.