ArticleThe Journal of biological chemistry2015
Cardiac Myosin-binding Protein C and Troponin-I Phosphorylation Independently Modulate Myofilament Length-dependent Activation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis.Frontiers in cardiovascular medicine · 2022Pooled it
- Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro.Journal of the American Heart Association · 2018Trial
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- 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
- GSK3β-driven phosphorylation of ABLIM1 regulates its interactions with titin cardiac muscle.The Journal of general physiology · 2025Article
- Myosin-binding protein C regulates the sarcomere lattice and stabilizes the OFF states of myosin heads.Nature communications · 2024Article
- Myosin-binding protein C forms C-links and stabilizes OFF states of myosin.bioRxiv : the preprint server for biology · 2023Article
- Thin filament regulation of cardiac muscle power output: Implications for targets to improve human failing hearts.The Journal of general physiology · 2023Article
- N-terminal truncated cardiac troponin I enhances Frank-Starling response by increasing myofilament sensitivity to resting tension.The Journal of general physiology · 2023Article
- Sarcomere length affects Ca2+ sensitivity of contraction in ischemic but not non-ischemic myocardium.The Journal of general physiology · 2023Article
- Myofilament Alterations Associated with Human R14del-Phospholamban Cardiomyopathy.International journal of molecular sciences · 2023Article
- Distinct Mechanisms for Increased Cardiac Contraction Through Selective Alteration of Either Myosin or Troponin Activity.JACC. Basic to translational science · 2022Article
- Cardiac efficiency and Starling's Law of the Heart.The Journal of physiology · 2022Article
- Work-loop contractions reveal that the afterload-dependent time course of cardiac CaJournal of applied physiology (Bethesda, Md. : 1985) · 2022Article
- The Acute Effects of Leptin on the Contractility of Isolated Rat Atrial and Ventricular Cardiomyocytes.International journal of molecular sciences · 2022Article
- Shortening the thick filament by partial deletion of titin's C-zone alters cardiac function by reducing the operating sarcomere length range.Journal of molecular and cellular cardiology · 2022Article
- GSK-3β Localizes to the Cardiac Z-Disc to Maintain Length Dependent Activation.Circulation research · 2022Article
- Modulation of myosin by cardiac myosin binding protein-C peptides improves cardiac contractility in ex-vivo experimental heart failure models.Scientific reports · 2022Article
- Striated muscle proteins are regulated both by mechanical deformation and by chemical post-translational modification.Biophysical reviews · 2021Review
- Cardiac MyBP-C phosphorylation regulates the Frank-Starling relationship in murine hearts.The Journal of general physiology · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
β-Adrenergic stimulation in heart leads to increased contractility and lusitropy via activation of protein kinase A (PKA). In the cardiac sarcomere, both cardiac myosin binding protein C (cMyBP-C) and troponin-I (cTnI) are prominent myofilament targets of PKA. Treatment of permeabilized myocardium with PKA induces enhanced myofilament length-dependent activation (LDA), the cellular basis of the Frank-Starling cardiac regulatory mechanism. It is not known, however, which of these targets mediates the altered LDA and to what extent. Here, we employed two genetic mouse models in which the three PKA sites in cMyBP-C were replaced with either phospho-mimic (DDD) or phospho-null (AAA) residues. AAA- or DDD-permeabilized myocytes (n = 12-17) were exchanged (~93%) for recombinant cTnI in which the two PKA sites were mutated to either phospho-mimic (DD) or phospho-null (AA) residues. Force-[Ca(2+)] relationships were determined at two sarcomere lengths (SL = 1.9 μm and SL = 2.3 μm). Data were fit to a modified Hill equation for each individual cell preparation at each SL. LDA was indexed as ΔEC50, the difference in [Ca(2+)] required to achieve 50% force activation at the two SLs. We found that PKA-mediated phosphorylation of cMyBP-C and cTnI each independently contribute to enhance myofilament length-dependent activation properties of the cardiac sarcomere, with relative contributions of ~67 and ~33% for cMyBP-C for cTnI, respectively. We conclude that β-adrenergic stimulation enhances the Frank-Starling regulatory mechanism predominantly via cMyBP-C PKA-mediated phosphorylation. We speculate that this molecular mechanism enhances cross-bridge formation at long SL while accelerating cross-bridge detachment and relaxation at short SLs.
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