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The effects of inorganic phosphate on muscle force development and energetics: challenges in modelling related to experimental uncertainties
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Linnaeus University, Linnaeus Knowledge Environments, Advanced Materials.ORCID iD: 0000-0002-5889-7792
2021 (English)In: Journal of Muscle Research and Cell Motility, ISSN 0142-4319, E-ISSN 1573-2657, Vol. 42, p. 33-46Article in journal (Refereed) Published
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Abstract [en]

Muscle force and power are developed by myosin cross-bridges, which cyclically attach to actin, undergo a force-generating transition and detach under turnover of ATP. The force-generating transition is intimately associated with release of inorganic phosphate (Pi) but the exact sequence of events in relation to the actual Pi release step is controversial. Details of this process are reflected in the relationships between [Pi] and the developed force and shortening velocity. In order to account for these relationships, models have proposed branched kinetic pathways or loose coupling between biochemical and force-generating transitions. A key hypothesis underlying the present study is that such complexities are not required to explain changes in the force-velocity relationship and ATP turnover rate with altered [Pi]. We therefore set out to test if models without branched kinetic paths and Pi-release occurring before the main force-generating transition can account for effects of varied [Pi] (0.1-25 mM). The models tested, one assuming either linear or non-linear cross-bridge elasticity, account well for critical aspects of muscle contraction at 0.5 mM Pi but their capacity to account for the maximum power output vary. We find that the models, within experimental uncertainties, account for the relationship between [Pi] and isometric force as well as between [Pi] and the velocity of shortening at low loads. However, in apparent contradiction with available experimental findings, the tested models produce an anomalous force-velocity relationship at elevated [Pi] and high loads with more than one possible velocity for a given load. Nevertheless, considering experimental uncertainties and effects of sarcomere non-uniformities, these discrepancies are insufficient to refute the tested models in favour of more complex alternatives.

Place, publisher, year, edition, pages
Springer, 2021. Vol. 42, p. 33-46
Keywords [en]
Myosin cross-bridges, Chemo-mechanical statistical model, Inorganic phosphate, Power, Force-velocity, Efficiency
National Category
Biophysics Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
URN: urn:nbn:se:lnu:diva-89864DOI: 10.1007/s10974-019-09558-2ISI: 000490631200002PubMedID: 31620962Scopus ID: 2-s2.0-85073997493Local ID: 2019OAI: oai:DiVA.org:lnu-89864DiVA, id: diva2:1366942
Available from: 2019-10-31 Created: 2019-10-31 Last updated: 2023-01-11Bibliographically approved

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Månsson, Alf

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