A stochastic simulation of skeletal muscle calcium transients in a structurally realistic sarcomere model using MCell

Skeletal muscle contraction is initiated when an action potential triggers the release of Ca(2+) into the sarcomere in a process referred to as excitation-contraction coupling. The speed and scale of this process makes direct observation very challenging and invasive. To determine how the concentration of Ca(2+) changes within the myofibril during a single activation, several simulation models have been developed. These models follow a common pattern; divide the half sarcomere into a series of compartments, then use ordinary differential equations to solve reactions occurring within and between the compartments. To further develop this type of simulation, we have created a realistic structural model of a skeletal muscle myofibrillar half-sarcomere using MCell software that incorporates the myofilament lattice structure. Using this simulation model, we were successful in reproducing the averaged calcium transient during a single activation consistent with both the experimental and previous simulation results. In addition, our simulation demonstrated that the inclusion of the myofilament lattice within our model produced an asymmetric distribution of Ca(2+), with more Ca(2+) accumulating near the Z-disk and less Ca(2+) reaching the m-line. This asymmetric distribution of Ca(2+) is also apparent when we examine how the Ca(2+) are bound to the troponin-C proteins along the actin filaments. Our simulation model also allowed us to produce advanced visualizations of this process, including two simulation animations, allowing us to view Ca(2+) release, diffusion, binding and uptake within the myofibrillar half-sarcomere.