ArticleProceedings of the National Academy of Sciences of the United States of America2021
Stress-dependent activation of myosin in the heart requires thin filament activation and thick filament mechanosensing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator.JCI insight · 2026Article
- Myosin motor dynamics and cardiac function: Insights from in vivo small-angle X-ray scattering and pressure-volume analysis.The Journal of physiology · 2026Article
- Titin's P-zone domains A164-167 are essential for thick filament structural arrangement.The Journal of general physiology · 2026Article
- Lipid droplets are rigid and physically suppress phagocytosis, unless cell compression or stretching activates actomyosin.Molecular biology of the cell · 2026Article
- Spatial control of myosin regulatory light chain phosphorylation modulates cardiac thick filament mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Human atrial skinned muscle fibers exhibit reduced length-dependent activation but show faster force development kinetics than ventricular muscle.Journal of molecular and cellular cardiology · 2026Article
- Cardiac myosin-binding protein-C acts as a tunable load sensor to regulate afterload dependence of ventricular function.American journal of physiology. Heart and circulatory physiology · 2025Article
- A new era of understanding of the control of thick filament states in the heartbeat.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Myosin-actin crossbridge independent sarcomere length induced CaJournal of molecular and cellular cardiology · 2025Article
- Connecting developed pressure - Preload relationship in ex-vivo beating heart with cellular sarcomere length - Tension relationship.Journal of biomechanics · 2025Article
- Modeling cardiac contractile cooperativity across species.The Journal of general physiology · 2025Article
- A Drosophila cardiac myosin increases jump muscle stretch activation and shortening deactivation.Biophysical journal · 2025Article
- Functional control of myosin motors in the cardiac cycle.Nature reviews. Cardiology · 2025Review
- Early pathological mechanisms in a mouse model of heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2024Article
- Load-dependence of the activation of myosin filaments in heart muscle.The Journal of physiology · 2024Article
- Calcium has a direct effect on thick filament activation in porcine myocardium.The Journal of general physiology · 2024Article
- Cardiac length-dependent activation driven by force-dependent thick-filament dynamics.Biophysical journal · 2024Article
- Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle.International journal of molecular sciences · 2024Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Myosin-based regulation in the heart muscle modulates the number of myosin motors available for interaction with calcium-regulated thin filaments, but the signaling pathways mediating the stronger contraction triggered by stretch between heartbeats or by phosphorylation of the myosin regulatory light chain (RLC) remain unclear. Here, we used RLC probes in demembranated cardiac trabeculae to investigate the molecular structural basis of these regulatory pathways. We show that in relaxed trabeculae at near-physiological temperature and filament lattice spacing, the RLC-lobe orientations are consistent with a subset of myosin motors being folded onto the filament surface in the interacting-heads motif seen in isolated filaments. The folded conformation of myosin is disrupted by cooling relaxed trabeculae, similar to the effect induced by maximal calcium activation. Stretch or increased RLC phosphorylation in the physiological range have almost no effect on RLC conformation at a calcium concentration corresponding to that between beats. These results indicate that in near-physiological conditions, the folded myosin motors are not directly switched on by RLC phosphorylation or by the titin-based passive tension at longer sarcomere lengths in the absence of thin filament activation. However, at the higher calcium concentrations that activate the thin filaments, stretch produces a delayed activation of folded myosin motors and force increase that is potentiated by RLC phosphorylation. We conclude that the increased contractility of the heart induced by RLC phosphorylation and stretch can be explained by a calcium-dependent interfilament signaling pathway involving both thin filament sensitization and thick filament mechanosensing.
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