A multiscale computational model of spatially resolved calcium cycling in cardiac myocytes: from detailed cleft dynamics to the whole cell concentration profiles

• Main Authors: Janine eVierheller, Wilhelm eNeubert, Martin eFalcke, Stephen Henry Gilbert, Nagaiah eChamakuri
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2015-09-01
• Series: Frontiers in Physiology
• Subjects: cardiomyocyte; calcium cycling; FEM; Dyad; stochastic spatially resolved cell models
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fphys.2015.00255/full

Mathematical modelling of excitation-contraction coupling (ECC) in ventricular cardiac myocytes is a multiscale problem, and it is therefore difficult to develop spatially detailed simulation tools. ECC involves gradients on the length scale of 100 nm in dyadic spaces and concentration profiles along the 100 □m of the whole cell, as well as the sub-millisecond time scale of local concentration changes and the change of lumenal Ca2+ content within tens of seconds. Our concept for a multiscale mathematical model of Ca2+ -induced Ca2+ release (CICR) and whole cardiomyocyte electrophysiology incorporates stochastic simulation of individual LC- and RyR-channels, spatially detailed concentration dynamics in dyadic clefts, rabbit membrane potential dynamicsand a system of partial differential equations for myoplasmic and lumenal free Ca2+ and Ca2+-binding molecules in the bulk of the cell. We developed a novel computational approach to resolve the concentration gradients from dyadic space to cell level by using a quasistatic approximation within the dyad and finite element methods for integrating the partial differential equations.