ArticleThe Journal of physiology2004
Roles of phosphorylation of myosin binding protein-C and troponin I in mouse cardiac muscle twitch dynamics.
Article in The Journal of physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
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- Synthetic growth hormone-releasing hormone agonist ameliorates the myocardial pathophysiology characteristic of heart failure with preserved ejection fraction.Cardiovascular research · 2023Article
- Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling.Quarterly reviews of biophysics · 2023Review
- Ion Channel Impairment and Myofilament CaCells · 2021Review
- Effect of transient elevation of glucose on contractile properties in non-diabetic rat cardiac muscle.Heart and vessels · 2021Article
- Cardiac Myosin Binding Protein-C Phosphorylation Mitigates Age-Related Cardiac Dysfunction: Hope for Better Aging?JACC. Basic to translational science · 2019Article
- NOX Inhibition Improves β-Adrenergic Stimulated Contractility and Intracellular Calcium Handling in the Aged Rat Heart.International journal of molecular sciences · 2018Article
- Posttranslational modifications of calcium/calmodulin-dependent protein kinase IIδ and its downstream signaling in human failing hearts.American journal of translational research · 2017Article
- Acute Optogenetic Modulation of Cardiac Twitch Dynamics Explored Through Modeling.Journal of biomechanical engineering · 2016Article
- Dysferlin deficiency blunts β-adrenergic-dependent lusitropic function of mouse heart.The Journal of physiology · 2015Article
- CaMKII-dependent myofilament Ca2+ desensitization contributes to the frequency-dependent acceleration of relaxation.Cell calcium · 2015Article
- Contractile apparatus dysfunction early in the pathophysiology of diabetic cardiomyopathy.World journal of diabetes · 2015Review
- Phosphorylation of cardiac Myosin-binding protein-C is a critical mediator of diastolic function.Circulation. Heart failure · 2015Article
- Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or β1-Adrenergic Stimulation.Circulation. Heart failure · 2015Article
- Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose.American journal of physiology. Heart and circulatory physiology · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
A normal heart increases its contractile force with increasing heart rate. Although calcium handling and myofibrillar proteins have been implicated in maintaining this positive force-frequency relationship (FFR), the exact mechanisms by which it occurs have not been addressed. In this study, we have developed an analytical method to define the calcium-force loop data, which characterizes the function of the contractile proteins in response to calcium that is independent of the calcium handling proteins. Results demonstrate that increasing the stimulation frequency causes increased force production per unit calcium concentration and decreased frequency-dependent calcium sensitivity during the relaxation phase. We hypothesize that phosphorylation of myosin binding protein-C (MyBP-C) and troponin I (TnI) acts coordinately to change the rates of force generation and relaxation, respectively. To test this hypothesis, we performed simultaneous calcium and force measurements on stimulated intact mouse papillary bundles before and after inhibition of MyBP-C and TnI phosphorylation using the calcium/calmodulin kinase II (CaMK2) inhibitor autocamtide-2 related inhibitory peptide, or the protein kinase A (PKA) inhibitor 14-22 amide. CaMK2 inhibition reduced both MyBP-C and TnI phosphorylation and decreased active force without changing the magnitude of the [Ca(2+)](i) transient. This reduced the normalized change in force per change in calcium by 19-39%. Data analyses demonstrated that CaMK2 inhibition changed the myofilament characteristics via a crossbridge feedback mechanism. These results strongly suggest that the phosphorylation of MyBP-C and TnI contributes significantly to the rates of force development and relaxation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.