Abstract
The ability for muscle to repeatedly generate force is limited by fatigue. The cellular mechanisms behind muscle fatigue are complex and potentially include breakdown at many points along the excitation–contraction pathway. In this paper we construct a mathematical model of the skeletal muscle excitation–contraction pathway based on the cellular biochemical events that link excitation to contraction. The model includes descriptions of membrane voltage, calcium cycling and crossbridge dynamics and was parameterised and validated using the response characteristics of mouse skeletal muscle to a range of electrical stimuli. This model was used to uncover the complexities of skeletal muscle fatigue. We also parameterised our model to describe force kinetics in fast and slow twitch fibre types, which have a number of biochemical and biophysical differences. How these differences interact to generate different force/fatigue responses in fast- and slow- twitch fibres is not well understood and we used our modelling approach to bring new insights to this relationship.
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Appendix 1 Model Equations
Appendix 1 Model Equations
Sarcolemma and t-tubule action potential generation
Two compartment model
where the function Zs is defined by
and the function Zt is defined by
PDE model
Ca2+ release from RyR’s
Ca2+ transport and XB dynamics
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Shorten, P.R., O’Callaghan, P., Davidson, J.B. et al. A mathematical model of fatigue in skeletal muscle force contraction. J Muscle Res Cell Motil 28, 293–313 (2007). https://doi.org/10.1007/s10974-007-9125-6
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DOI: https://doi.org/10.1007/s10974-007-9125-6