A Stochastic Simulation of Skeletal Muscle Calcium Transients in a Structurally Realistic Sarcomere Model using MCell

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dc.contributor.authorHolash, Robert John
dc.contributor.authorMacIntosh, Brian R.
dc.date.accessioned2019-02-08T19:33:01Z
dc.date.available2019-02-08T19:33:01Z
dc.date.issued2019-01-30
dc.descriptionData repository for a PLOS computational biology submissionen_US
dc.description.abstractSkeletal 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.en_US
dc.description.grantingagencyNatural Sciences and Engineering Research Council - Discovery Granten_US
dc.identifier.citationHolash, 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".en_US
dc.identifier.grantnumberRGPIN/05113-2015en_US
dc.identifier.urihttp://hdl.handle.net/1880/109891
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/36140
dc.language.isoenen_US
dc.publisherPLOS Computational Biologyen_US
dc.publisher.departmentHuman Performance Laben_US
dc.publisher.facultyKinesiologyen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.rightsUnless 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.en_US
dc.subjectMuscle Physiologyen_US
dc.subjectComputational Biologyen_US
dc.subjectSkeletal Muscleen_US
dc.subjectContractionen_US
dc.titleA Stochastic Simulation of Skeletal Muscle Calcium Transients in a Structurally Realistic Sarcomere Model using MCellen_US
dc.title.alternativeStochastic model of calcium diffusion in a 3d myofibrilen_US
dc.typedataseten_US
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