Key result
Exposure of individual skeletal muscle myofibrils to peroxynitrite or its donor SIN-1 decreased isometric force by ~50% due to an increased cross-bridge detachment rate.
Why the study?
The details of the acute effects of reactive oxygen and nitrogen species on skeletal muscle myosin-actin interactions are not known.
Exposure to peroxynitrite reduces skeletal muscle myofibrillar isometric force by approximately 50% due to an increased cross-bridge detachment rate.
Peroxynitrite may impair myofibrillar force in oxidative stress; leaves open relevance to human skeletal muscle dysfunction.
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 ( g app ) in combination with a conservation of the force redevelopment rate (k Tr ) 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.
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Persson et al. (2019) studied Skeletal muscle weakness associated with oxidative stress. Peroxynitrite (ONOO-) or ONOO- donor (SIN-1) was evaluated on Isometric force and contractile properties. Exposure of individual skeletal muscle myofibrils to peroxynitrite or its donor SIN-1 decreased isometric force by ~50% due to an increased cross-bridge detachment rate.
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