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  1. Article ; Online: Troponin T amino acid mutation (ΔK210) knock-in mice as a neonatal dilated cardiomyopathy model.

    Tanihata, Jun / Fujii, Teruyuki / Baba, Shunsuke / Fujimoto, Yoshitaka / Morimoto, Sachio / Minamisawa, Susumu

    Pediatric research

    2020  Volume 89, Issue 4, Page(s) 846–857

    Abstract: Background: Dilated cardiomyopathy (DCM) in children is often associated with poor morbidity and mortality and exhibits distinct pathological entities from those of adult DCM. Owing to the limited number of patients and the lack of a good animal model, ... ...

    Abstract Background: Dilated cardiomyopathy (DCM) in children is often associated with poor morbidity and mortality and exhibits distinct pathological entities from those of adult DCM. Owing to the limited number of patients and the lack of a good animal model, the molecular mechanisms underlying pediatric DCM remain poorly understood. The purpose of this study is to establish an animal model of neonatal DCM and identify early progression factors.
    Methods: Cardiac phenotypes and comprehensive gene expression profiles in homozygous ΔK210 knock-in (TNNT2
    Results: Immediately after birth, the cardiac weight in TNNT2
    Conclusions: TNNT2
    Impact: TNNT2
    MeSH term(s) Animals ; Animals, Newborn ; Cardiomyopathy, Dilated/genetics ; Disease Models, Animal ; Down-Regulation ; Echocardiography ; Gene Expression Profiling ; Heart Ventricles/physiopathology ; Homozygote ; Mice ; Mice, Transgenic ; Mutation ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Prognosis ; Troponin T/genetics ; Up-Regulation
    Chemical Substances Troponin T
    Language English
    Publishing date 2020-06-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 4411-8
    ISSN 1530-0447 ; 0031-3998
    ISSN (online) 1530-0447
    ISSN 0031-3998
    DOI 10.1038/s41390-020-1016-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Simultaneous imaging of local calcium and single sarcomere length in rat neonatal cardiomyocytes using yellow Cameleon-Nano140.

    Tsukamoto, Seiichi / Fujii, Teruyuki / Oyama, Kotaro / Shintani, Seine A / Shimozawa, Togo / Kobirumaki-Shimozawa, Fuyu / Ishiwata, Shin'ichi / Fukuda, Norio

    The Journal of general physiology

    2016  Volume 148, Issue 4, Page(s) 341–355

    Abstract: In cardiac muscle, contraction is triggered by sarcolemmal depolarization, resulting in an intracellular Ca(2+) transient, binding of Ca(2+) to troponin, and subsequent cross-bridge formation (excitation-contraction [EC] coupling). Here, we develop a ... ...

    Abstract In cardiac muscle, contraction is triggered by sarcolemmal depolarization, resulting in an intracellular Ca(2+) transient, binding of Ca(2+) to troponin, and subsequent cross-bridge formation (excitation-contraction [EC] coupling). Here, we develop a novel experimental system for simultaneous nano-imaging of intracellular Ca(2+) dynamics and single sarcomere length (SL) in rat neonatal cardiomyocytes. We achieve this by expressing a fluorescence resonance energy transfer (FRET)-based Ca(2+) sensor yellow Cameleon-Nano (YC-Nano) fused to α-actinin in order to localize to the Z disks. We find that, among four different YC-Nanos, α-actinin-YC-Nano140 is best suited for high-precision analysis of EC coupling and α-actinin-YC-Nano140 enables quantitative analyses of intracellular calcium transients and sarcomere dynamics at low and high temperatures, during spontaneous beating and with electrical stimulation. We use this tool to show that calcium transients are synchronized along the length of a myofibril. However, the averaging of SL along myofibrils causes a marked underestimate (∼50%) of the magnitude of displacement because of the different timing of individual SL changes, regardless of the absence or presence of positive inotropy (via β-adrenergic stimulation or enhanced actomyosin interaction). Finally, we find that β-adrenergic stimulation with 50 nM isoproterenol accelerated Ca(2+) dynamics, in association with an approximately twofold increase in sarcomere lengthening velocity. We conclude that our experimental system has a broad range of potential applications for the unveiling molecular mechanisms of EC coupling in cardiomyocytes at the single sarcomere level.
    MeSH term(s) Actinin/metabolism ; Animals ; Animals, Newborn ; Calcium/metabolism ; Luminescent Proteins/physiology ; Myocytes, Cardiac/cytology ; Nanotechnology ; Rats ; Sarcomeres/metabolism
    Chemical Substances Luminescent Proteins ; Actinin (11003-00-2) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2016-09-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3118-5
    ISSN 1540-7748 ; 0022-1295
    ISSN (online) 1540-7748
    ISSN 0022-1295
    DOI 10.1085/jgp.201611604
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: In vivo cardiac nano-imaging: A new technology for high-precision analyses of sarcomere dynamics in the heart.

    Shimozawa, Togo / Hirokawa, Erisa / Kobirumaki-Shimozawa, Fuyu / Oyama, Kotaro / Shintani, Seine A / Terui, Takako / Kushida, Yasuharu / Tsukamoto, Seiichi / Fujii, Teruyuki / Ishiwata, Shin'ichi / Fukuda, Norio

    Progress in biophysics and molecular biology

    2017  Volume 124, Page(s) 31–40

    Abstract: The cardiac pump function is a result of a rise in intracellular ... ...

    Abstract The cardiac pump function is a result of a rise in intracellular Ca
    MeSH term(s) Animals ; Calcium/metabolism ; Humans ; Intracellular Space/metabolism ; Molecular Imaging/methods ; Nanotechnology/methods ; Sarcomeres/metabolism
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2017-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 209302-9
    ISSN 1873-1732 ; 0079-6107
    ISSN (online) 1873-1732
    ISSN 0079-6107
    DOI 10.1016/j.pbiomolbio.2016.09.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Depressed Frank-Starling mechanism in the left ventricular muscle of the knock-in mouse model of dilated cardiomyopathy with troponin T deletion mutation ΔK210.

    Inoue, Takahiro / Kobirumaki-Shimozawa, Fuyu / Kagemoto, Tatsuya / Fujii, Teruyuki / Terui, Takako / Kusakari, Yoichiro / Hongo, Kenichi / Morimoto, Sachio / Ohtsuki, Iwao / Hashimoto, Kazuhiro / Fukuda, Norio

    Journal of molecular and cellular cardiology

    2013  Volume 63, Page(s) 69–78

    Abstract: It has been reported that the Frank-Starling mechanism is coordinately regulated in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice spacing changes. In the present study, we tested the hypothesis that the deletion mutation ... ...

    Abstract It has been reported that the Frank-Starling mechanism is coordinately regulated in cardiac muscle via thin filament "on-off" equilibrium and titin-based lattice spacing changes. In the present study, we tested the hypothesis that the deletion mutation ΔK210 in the cardiac troponin T gene shifts the equilibrium toward the "off" state and accordingly attenuate the sarcomere length (SL) dependence of active force production, via reduced cross-bridge formation. Confocal imaging in isolated hearts revealed that the cardiomyocytes were enlarged, especially in the longitudinal direction, in ΔK210 hearts, with striation patterns similar to those in wild type (WT) hearts, suggesting that the number of sarcomeres is increased in cardiomyocytes but the sarcomere length remains unaltered. For analysis of the SL dependence of active force, skinned muscle preparations were obtained from the left ventricle of WT and knock-in (ΔK210) mice. An increase in SL from 1.90 to 2.20μm shifted the mid-point (pCa50) of the force-pCa curve leftward by ~0.21pCa units in WT preparations. In ΔK210 muscles, Ca(2+) sensitivity was lower by ~0.37pCa units, and the SL-dependent shift of pCa50, i.e., ΔpCa50, was less pronounced (~0.11pCa units), with and without protein kinase A treatment. The rate of active force redevelopment was lower in ΔK210 preparations than in WT preparations, showing blunted thin filament cooperative activation. An increase in thin filament cooperative activation upon an increase in the fraction of strongly bound cross-bridges by MgADP increased ΔpCa50 to ~0.21pCa units. The depressed Frank-Starling mechanism in ΔK210 hearts is the result of a reduction in thin filament cooperative activation.
    MeSH term(s) Adenosine Diphosphate/metabolism ; Animals ; Calcium/metabolism ; Cardiomyopathy, Dilated/genetics ; Cardiomyopathy, Dilated/physiopathology ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Disease Models, Animal ; Heart Ventricles/metabolism ; Heart Ventricles/physiopathology ; In Vitro Techniques ; Mice ; Mice, Transgenic ; Myocardial Contraction/genetics ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Sequence Deletion ; Troponin T/genetics ; Troponin T/metabolism
    Chemical Substances Troponin T ; Adenosine Diphosphate (61D2G4IYVH) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2013-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80157-4
    ISSN 1095-8584 ; 0022-2828
    ISSN (online) 1095-8584
    ISSN 0022-2828
    DOI 10.1016/j.yjmcc.2013.07.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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