The effect of mitochondria in intracellular calcium dynamics in cardiomyocytes: A simulation study

Abstract

Intracellular calcium (Cai) regulation in cardiomyocytes is critical because of its relationship with cell contractility and arrhythmogenesis. Although the mitochondria play an important role in Cai regulation, few action potential (AP) models include these organelles. In this work, we have included mitochondria in an AP model of a rabbit cardiomyocyte to study its influence in Cairegulation. The model includes the calcium uniporter, the sodium-calcium exchanger and intra-mitochondrial calcium buffering. We conducted simulations in which Caibiomarkers were compared in the presence and in the absence of mitochondria. In some simulations, ionic currents were altered to simulate pharmacological interventions and/or the effect of mutations. Our results suggest that the absence of mitochondria in AP models introduces significant errors in the simulation of Caihandling, especially under conditions of altered currents.