ArticleBiophysical journal2011
Enhanced active cross-bridges during diastole: molecular pathogenesis of tropomyosin's HCM mutations.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 67 citations in OpenAlex.
- Heart Failure in Hypertrophic Cardiomyopathy.Cardiac failure review · 2026Review
- Evaluating Pathogenicity ofJournal of precision medicine (Amsterdam, Netherlands) · 2025Article
- The elementary step that generates force and sinusoidal analysis in striated muscle fibers.Journal of muscle research and cell motility · 2025Review
- Creatine Kinase Equilibration and ΔGInternational journal of molecular sciences · 2023Article
- Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L.PNAS nexus · 2023Article
- The effect of gender and obesity in modulating cross-bridge function in cardiac muscle fibers.Journal of muscle research and cell motility · 2022Article
- Critical Evaluation of Current Hypotheses for the Pathogenesis of Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2022Review
- Generative adversarial networks for construction of virtual populations of mechanistic models: simulations to study Omecamtiv Mecarbil action.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.Frontiers in cardiovascular medicine · 2022Review
- Computational and biophysical determination of pathogenicity of variants of unknown significance in cardiac thin filament.JCI insight · 2021Article
- Cardiomyocyte Dysfunction in Inherited Cardiomyopathies.International journal of molecular sciences · 2021Review
- Single-molecule imaging reveals the concerted release of myosin from regulated thin filaments.eLife · 2021Article
- Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation.The Journal of general physiology · 2021Article
- A Stochastic Multiscale Model of Cardiac Thin Filament Activation Using Brownian-Langevin Dynamics.Biophysical journal · 2019Article
- Cardiomyopathy-associated mutations in tropomyosin differently affect actin-myosin interaction at single-molecule and ensemble levels.Journal of muscle research and cell motility · 2019Review
- The R249Q hypertrophic cardiomyopathy myosin mutation decreases contractility in Drosophila by impeding force production.The Journal of physiology · 2019Article
- Functional significance of HCM mutants of tropomyosin, V95A and D175N, studied withBiophysics and physicobiology · 2019Article
- Pathogenesis of Hypertrophic Cardiomyopathy is Mutation Rather Than Disease Specific: A Comparison of the Cardiac Troponin T E163R and R92Q Mouse Models.Journal of the American Heart Association · 2017Article
- The functional significance of the last 5 residues of the C-terminus of cardiac troponin I.Archives of biochemistry and biophysics · 2016Article
- Effect of N-Terminal Extension of Cardiac Troponin I on the Ca(2+) Regulation of ATP Binding and ADP Dissociation of Myosin II in Native Cardiac Myofibrils.Biochemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Three HCM-causing tropomyosin (Tm) mutants (V95A, D175N, and E180G) were examined using the thin-filament extraction and reconstitution technique. The effects of Ca(2+), ATP, phosphate, and ADP concentrations on cross-bridge kinetics in myocardium reconstituted with each of these mutants were studied at 25°C, and compared to wild-type (WT) Tm at physiological ionic strength (200 mM). All three mutants showed significantly higher (2-3.5 fold) low Ca(2+) tension (T(LC)) and stiffness than WT at pCa 8.0. High Ca(2+) tension (T(HC)) was significantly higher for E180G than that for WT, whereas T(HC) of V95A and D175N was similar to WT; high Ca(2+) stiffness (Y(HC)) had the same trend. The Ca(2+) sensitivity of isometric force was significantly greater for V95A and E180G than for WT, whereas that of D175N remained the same as for WT; for all mutants, cooperativity was lower than for WT. Nine kinetic constants and the cross-bridge distribution were deduced using sinusoidal analysis. The number of force-generating cross bridges was similar among the D175N, E180G, and WT Tm forms, but it was significantly larger in the case of V95A than WT. We conclude that the increased number of actively cycling cross bridges at pCa 8 is the major cause of Tm mutation-related HCM pathogenesis, which may result in diastolic dysfunction. Decreased contractility (T(act)) in V95A and D175N may further contribute to the severity of myocyte hypertrophy and related prognosis of the disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.