title: The Role of Parvalbumin, Sarcoplasmatic Reticulum Calcium Pump Rate, Rates of Cross-Bridge Dynamics, and Ryanodine Receptor Calcium Current on Peripheral Muscle Fatigue: A Simulation Study.
abstract: A biophysical model of the excitation-contraction pathway, which has previously been validated for slow-twitch and fast-twitch skeletal muscles, is employed to investigate key biophysical processes leading to peripheral muscle fatigue. Special emphasis hereby is on investigating how the model's original parameter sets can be interpolated such that realistic behaviour with respect to contraction time and fatigue progression can be obtained for a continuous distribution of the model's parameters across the muscle units, as found for the functional properties of muscles. The parameters are divided into 5 groups describing (i) the sarcoplasmatic reticulum calcium pump rate, (ii) the cross-bridge dynamics rates, (iii) the ryanodine receptor calcium current, (iv) the rates of binding of magnesium and calcium ions to parvalbumin and corresponding dissociations, and (v) the remaining processes. The simulations reveal that the first two parameter groups are sensitive to contraction time but not fatigue, the third parameter group affects both considered properties, and the fourth parameter group is only sensitive to fatigue progression. Hence, within the scope of the underlying model, further experimental studies should investigate parvalbumin dynamics and the ryanodine receptor calcium current to enhance the understanding of peripheral muscle fatigue.
authors.affiliation: Institute of Applied Mechanics (CE), University of Stuttgart, Stuttgart, Germany; Stuttgart Research Centre for Simulation Technology (SimTech), University of Stuttgart, Stuttgart, Germany.
authors.forename: Oliver
authors.identifier: 0000-0002-1934-6525
authors.initials: O
authors.lastname: Röhrle
authors.affiliation: Institute of Applied Mechanics (CE), University of Stuttgart, Stuttgart, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Neumann
authors.affiliation: Institute of Applied Mechanics (CE), University of Stuttgart, Stuttgart, Germany; Stuttgart Research Centre for Simulation Technology (SimTech), University of Stuttgart, Stuttgart, Germany.
authors.forename: Thomas
authors.identifier: 0000-0001-9381-1598
authors.initials: T
authors.lastname: Heidlauf
mesh_terms: D000818:Animals; D002118:Calcium / Q000737:chemistry*; D003198:Computer Simulation; D018450:Disease Progression; D006801:Humans; D007477:Ions; D008274:Magnesium / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D008962:Models, Theoretical; D018763:Muscle Fatigue; D009124:Muscle Proteins / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D010320:Parvalbumins / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D015203:Reproducibility of Results; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000502:physiology*
chemical_list: D007477:Ions; D009124:Muscle Proteins; D010320:Parvalbumins; D020033:Protein Isoforms; D019837:Ryanodine Receptor Calcium Release Channel; D008274:Magnesium; D002118:Calcium