ArticleThe Journal of physiology2005
Effects of the mutation R145G in human cardiac troponin I on the kinetics of the contraction-relaxation cycle in isolated cardiac myofibrils.
Article in The Journal of physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Troponin I - a comprehensive review of its function, structure, evolution, and role in muscle diseases.Animal cells and systems · 2025Review
- Focus on cardiac troponin complex: From gene expression to cardiomyopathy.Genes & diseases · 2024Review
- Assessing Cardiac Contractility From Single Molecules to Whole Hearts.JACC. Basic to translational science · 2024Review
- Force Measurements From Myofibril to Filament.Frontiers in physiology · 2021Review
- Troponin structure and function: a view of recent progress.Journal of muscle research and cell motility · 2020Review
- New insights provided by myofibril mechanics in inherited cardiomyopathies.Conditioning medicine · 2019Article
- Restrictive Cardiomyopathy Troponin I R145W Mutation Does Not Perturb Myofilament Length-dependent Activation in Human Cardiac Sarcomeres.The Journal of biological chemistry · 2016Article
- Effects of Cardiac Troponin I Mutation P83S on Contractile Properties and the Modulation by PKA-Mediated Phosphorylation.The journal of physical chemistry. B · 2016Article
- Order-Disorder Transitions in the Cardiac Troponin Complex.Journal of molecular biology · 2016Review
- Force per cross-sectional area from molecules to muscles: a general property of biological motors.Royal Society open science · 2016Article
- Cardiac troponin structure-function and the influence of hypertrophic cardiomyopathy associated mutations on modulation of contractility.Archives of biochemistry and biophysics · 2016Review
- Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype.Frontiers in physiology · 2016Review
- Why Is there a Limit to the Changes in Myofilament CaFrontiers in physiology · 2016Review
- Troponin I Mutations R146G and R21C Alter Cardiac Troponin Function, Contractile Properties, and Modulation by Protein Kinase A (PKA)-mediated Phosphorylation.The Journal of biological chemistry · 2015Article
- Effects of HCM cTnI mutation R145G on troponin structure and modulation by PKA phosphorylation elucidated by molecular dynamics simulations.Biophysical journal · 2015Article
- Deletion of the titin N2B region accelerates myofibrillar force development but does not alter relaxation kinetics.Journal of cell science · 2014Article
- Ca(2+)-regulatory function of the inhibitory peptide region of cardiac troponin I is aided by the C-terminus of cardiac troponin T: Effects of familial hypertrophic cardiomyopathy mutations cTnI R145G and cTnT R278C, alone and in combination, on filament sliding.Archives of biochemistry and biophysics · 2014Article
- Structural and functional consequences of cardiac troponin C L57Q and I61Q Ca(2+)-desensitizing variants.Archives of biochemistry and biophysics · 2013Article
- Mechanical and energetic properties of papillary muscle from ACTC E99K transgenic mouse models of hypertrophic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2013Article
- Engineered troponin C constructs correct disease-related cardiac myofilament calcium sensitivity.The Journal of biological chemistry · 2012Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Familial hypertrophic cardiomyopathy (FHC) has been linked to mutations in sarcomeric proteins such as human cardiac troponin I (hcTnI). To elucidate the functional consequences of the mutation hcTnI(R145G) on crossbridge kinetics, force kinetics were analysed in murine cardiac myofibrils carrying either the mutant or the wild-type protein. The mutation was introduced into the myofibrils in two different ways: in the first approach, the endogenous Tn was replaced by incubation of the myofibrils with an excess of reconstituted recombinant hcTn containing either hcTnI(WT) or hcTnI(R145G). Alternatively, myofibrils were isolated either from non-transgenic or transgenic mice expressing the corresponding mcTnI(R146G) mutation. In myofibrils from both models, the mutation leads to a significant upward shift of the passive force-sarcomere length relation determined at pCa 7.5. Addition of 5 mm BDM (2,3-butandione-2-monoxime), an inhibitor of actomyosin ATPase partially reverses this shift, suggesting that the mutation impairs the normal function of cTnI to fully inhibit formation of force-generating crossbridges in the absence of Ca(2)(+). Maximum force development (F(max)) is significantly decreased by the mutation only in myofibrils exchanged with hcTnI(R145G) in vitro. Ca(2)(+) sensitivity of force development was reduced by the mutation in myofibrils from transgenic mice but not in exchanged myofibrils. In both models the rate constant of force development k(ACT) is reduced at maximal [Ca(2)(+)] but not at low [Ca(2)(+)] where it is rather increased. Force relaxation is significantly prolonged due to a reduction of the relaxation rate constant k(REL). We therefore assume that the impairment in the regulatory function of TnI by the mutation leads to modulations in crossbridge kinetics that significantly alter the dynamics of myofibrillar contraction and relaxation.
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