Copyright © 2012 Luyao Lu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cardiac cells with heart failure are usually characterized by impairment of Ca²⁺ handling with smaller SR Ca²⁺ store and high risk of triggered activities. In this study, we developed a coupled model by integrating the spatiotemporal Ca²⁺ reaction-diffusion system into the cellular electrophysiological model. With the coupled model, the subcellular Ca²⁺ dynamics and global cellular electrophysiology could be simultaneously traced. The proposed coupled model was then applied to study the effects of rogue RyRs on Ca²⁺ cycling and membrane potential in failing heart. The simulation results suggested that, in the presence of rogue RyRs, Ca²⁺ dynamics is unstable and Ca²⁺ waves are prone to be initiated spontaneously. These release events would elevate the membrane potential substantially which might induce delayed afterdepolarizations or triggered action potentials. Moreover, the variation of membrane potential depolarization is indicated to be dependent on the distribution density of rogue RyR channels. This study provides a new possible arrhythmogenic mechanism for heart failure from subcellular to cellular level.