Force generated by myosin cross-bridges is reduced in myofibrils exposed to ROS/RNS

Malin Persson, Maarten M. Steinz, Håkan Westerblad, Johanna T. Lanner, Dilson E. Rassier

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Skeletal muscle weakness is associated with oxidative stress and oxidative posttranslational modifications on contractile proteins. There is indirect evidence that reactive oxygen/nitrogen species (ROS/RNS) affect skeletal muscle myofibrillar function, although the details of the acute effects of ROS/RNS on myosin-actin interactions are not known. In this study, we examined the effects of peroxynitrite (ONOO-) on the contractile properties of individual skeletal muscle myofibrils by monitoring myofibril-induced displacements of an atomic force cantilever upon activation and relaxation. The isometric force decreased by ~50% in myofibrils treated with the ONOO- donor (SIN-1) or directly with ONOO-, which was independent of the cross-bridge abundancy condition (i.e., rigor or relaxing condition) during SIN-1 or ONOO- treatment. The force decrease was attributed to an increase in the cross-bridge detachment rate (gapp) in combination with a conservation of the force redevelopment rate (kTr) and hence, an increase in the population of cross-bridges transitioning from force-generating to non-force-generating cross-bridges during steady-state. Taken together, the results of this study provide important information on how ROS/RNS affect myofibrillar force production which may be of importance for conditions where increased oxidative stress is part of the pathophysiology.

Original languageEnglish
Pages (from-to)C1304-C1312
JournalAmerican Journal of Physiology - Cell Physiology
Issue number6
Publication statusPublished - 1 Jan 2019
Externally publishedYes


  • Cross-bridges
  • Myofibrils
  • Oxidative stress
  • Peroxynitrite
  • Skeletal muscle

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