Holash, Robert JohnMacIntosh, Brian R.2019-02-082019-02-082019-01-30Holash, R. J., & MacIntosh, B. R. (2019). A Stochastic Simulation of Skeletal Muscle Calcium Transients in a Structurally Realistic Sarcomere Model using MCell. "PLOS Computational Biology".http://hdl.handle.net/1880/109891https://dx.doi.org/10.11575/PRISM/36140Data repository for a PLOS computational biology submissionSkeletal muscle contraction is initiated when an action potential triggers the release of Ca2+ 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 Ca2+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 Ca2+, with more Ca2+ accumulating near the Z-disk and less Ca2+ reaching the m-line. This asymmetric distribution of Ca2+ is apparent when we examine how the Ca2+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 Ca2+ release, diffusion, binding and uptake within the myofibrillar half-sarcomere.enUnless otherwise indicated, this material is protected by copyright and has been made available with authorization from the copyright owner. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Muscle PhysiologyComputational BiologySkeletal MuscleContractiondatasetRGPIN/05113-2015