Simulation of the Submembrane Calcium Diffusion in Cardiac Cells

Abstract

Intracellular calcium plays a major role in the electromechanical coupling in cardiac venrticular cells and in the action potential formation process in heart pacemaker cells. Calcium sparks are elementary events of the calcium release from sarcoplasmic reticulum taking place in submembrane space. Here we introduce a novel method of the computer simulations of the submembrane calcium diffusion in heart cells. We reproduce the results of the experiments on calcium sparks formation process in a single calcium release unit taking into account the stochastic dynamics of RyR-channels which are responsible for the calcium release. RyR dynamics is described within the framework of the previously developed electron-conformational model, which is integrated into the calcium dynamics model in the cardiac pacemaker cell. Our method gives the opportunity to describe the process of RyRs activation-deactivation in the macromolecular scale. Here we present results of the modelling of calcium diffusion in the dyadic space and “domino-like” RyR’s activation during the so-called “calcium induced calcium release process We conduct computer experiments to investigate $Ca^{2+}$ sparks initiation, spread and termination. The dependence of the sparks’ initiation and termination rate on the $Ca^{2+}$ diffusion velocity is investigated. We conclude that the main reason of the $Ca^{2+}$ spark termination can be the local depletion of the lumen of sarcoplasmic reticulum and RyR’s stochastic attrition.