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Myosin Cross-Bridges Do Not Form Precise Rigor Bonds in Hypertrophic Heart Muscle Carrying Troponin T Mutations

Title: Myosin Cross-Bridges Do Not Form Precise Rigor Bonds in Hypertrophic Heart Muscle Carrying Troponin T Mutations.
Name(s): Midde, K., author
Dumka, V., author
Pinto, Jose, author
Muthu, P., author
Marandos, P., author
Gryczynski, I., author
Gryczynski, Z., author
Potter, James, author
Borejdo, J., author
Type of Resource: text
Genre: Text
Issuance: serial
Date Issued: 2011
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Distribution of orientations of myosin was examined in ex-vivo myofibrils from hearts of transgenic (Tg) mice expressing Familial Hypertrophic Cardiomyopathy (FHC) troponin T (TnT) mutations I79N, F110I and R278C. Humans are heterozygous for sarcomeric FHC mutations and so hypertrophic myocardium contains a mixture of the wild-type (WT) and mutated (MUT) TnT. If mutations are expressed at a low level there may not be a significant change in the global properties of heart muscle. In contrast, measurements from a few molecules avoid averaging inherent in the global measurements. It is thus important to examine the properties of only a few molecules of muscle. To this end, the lever arm of one out of every 60,000 myosin molecules was labeled with a fluorescent dye and a small volume within the A-band (~1 fL) was observed by confocal microscopy. This volume contained on average 5 fluorescent myosin molecules. The lever arm assumes different orientations reflecting different stages of acto-myosin enzymatic cycle. We measured the distribution of these orientations by recording polarization of fluorescent light emitted by myosin-bound fluorophore during rigor and contraction. The distribution of orientations of rigor WT and MUT myofibrils was significantly different. There was a large difference in the width and of skewness and kurtosis of rigor distributions. These findings suggest that the hypertrophic phenotype associated with the TnT mutations can be characterized by a significant increase in disorder of rigor cross-bridges.
Identifier: FSU_migr_biomed_faculty_publications-0055 (IID), 10.1016/j.yjmcc.2011.06.001 (DOI)
Keywords: Cardiac Hypertrophy, Troponin T, polarization of fluorescence, confocal microscopy
Uncontrolled subjects: Animals, Cardiomyopathy, Hypertrophic, Familial, Humans, Mice, Mice, Transgenic, Muscle Tonus, Mutation, Myocardium, Myofibrils, Myosins, Troponin T
Note: Originally published in Journal'>">Journal of Molecular and Cellular Cardiology.
Citation: Midde K, Dumka V, Pinto JR, Muthu P, Marandos P, Gryczynski I, Gryczynski Z, Potter JD, & Borejdo J. (2011). Myosin cross-bridges do not form precise rigor bonds in hypertrophic heart muscle carrying troponin T mutations. J Mol Cell Cardiol, Sep;51(3):409-18. doi: 10.1016/j.yjmcc.2011.06.001.
Subject(s): Amino acids
Cardiovascular system -- Diseases
Cardiovascular system
Genetic aspects
Genetic disorders
Medical sciences
Musculoskeletal system
Persistent Link to This Record:
Owner Institution: FSU
Is Part of Series: Department of Biomedical Sciences Faculty Publications.
Is Part Of: Journal of Molecular and Cellular Cardiology.
Issue: 3, 51

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Midde, K., Dumka, V., Pinto, J., Muthu, P., Marandos, P., Gryczynski, I., … Borejdo, J. (2011). Myosin Cross-Bridges Do Not Form Precise Rigor Bonds in Hypertrophic Heart Muscle Carrying Troponin T Mutations. Journal Of Molecular And Cellular Cardiology. Retrieved from