Extracellular calcium and L-type calcium current inactivation mechanisms: A computational study

Extracellular calcium concentration ([Ca²⁺]_o) affects cardiac action potential (AP): their inverse dependence has already been assessed in vivo and in vitro. Both shortening and prolongation of AP are associated with an increased risk of arrhythmias and Ca²⁺ variations may occur in many different contexts (e.g. pathological hypo/hypercalcemia, haemodialysis therapy, bed-rest experiments). Computational modeling could provide a useful support to investigate this phenomenon: however, [Ca²⁺]₀ dependence is not reproduced properly by most of the commonly used human AP models The aim of this study has been to modify one of the most recent human ventricular cell model in order to improve its response to [Ca²⁺]₀ changes. The modified model has been validated against the same experimental data used for the original one, in order to verify its consistency, and it can thus be used to explore "in silico" the effects of electrolyte unbalances on the electrical activity of human cardiomyocytes.