ArticleThe Journal of physiology2024
Load-dependence of the activation of myosin filaments in heart muscle.
Article in The Journal of physiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Kinetic modeling of mant-ATP turnover to interpret the biochemically defined myosin SRX state.Biophysical journal · 2026Article
- Distinct distributions of myosin motor conformations during contraction of slow and fast skeletal muscle.The Journal of physiology · 2026Article
- Comparison of Predicted X-Ray Fiber Diffraction Patterns from All-Atom and Coarse-Grained Actin Filament Models Under Nonuniform Strain.International journal of molecular sciences · 2025Article
- Resolving zone-specific regulation of cardiac myosin.The Journal of general physiology · 2025Article
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Authors and funding
13 authors.
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Abstract
Contraction of heart muscle requires activation of both the actin and myosin filaments. The mechanism of myosin filament activation is unknown, but the leading candidate hypothesis is direct mechano-sensing by the filaments. Here, we tested this hypothesis by activating intact trabeculae from rat heart by electrical stimulation under different loads and measuring myosin filament activation by X-ray diffraction. Unexpectedly, we found that the distinct structural changes in the myosin filament associated with activation had different dependences on the load. In early activation, all the structural changes indicated faster activation at higher load, as expected from the mechano-sensing hypothesis, but, at later times, the helical order of the myosin motors characteristic of the inactivated state was lost even at very low load. We conclude that mechano-sensing does operate in heart muscle, but it is supplemented by a previously undescribed mechanism that links myosin filament activation to actin filament activation. KEY POINTS: Myosin filament activation controls the strength and speed of contraction in heart muscle. Early activation of the myosin filament is determined by the filament load. At later times, myosin filament activation is controlled by a load independent pathway. This load independent pathway provides new targets and assays for drug development.
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