Titin-based regulations of diastolic and systolic functions of mammalian cardiac muscle

Norio Fukuda, Takako Terui, Shin'ichi Ishiwata, Satoshi Kurihara

    Research output: Contribution to journalArticle

    33 Citations (Scopus)

    Abstract

    Titin is the largest protein in mammals; it forms an elastic filament along the myofibril of cardiac and skeletal muscles. Novel studies employing the recently available varied technologies have revealed the molecular mechanisms by which titin generates passive force in the sarcomere in response to external stretch. Changes in titin stiffness occur during heart disease via a shift in the expression ratio of the two main titin isoforms, called N2B (stiff type) and N2BA (compliant type) titins. Protein kinase (PK)A, PKG and PKC phosphorylate the cardiac specific I-band titin segment, resulting in an acute decrease (by PKA and PKG) or increase (by PKC) in passive force. It has also been discovered that titin performs roles that go beyond passive force generation, by enhancing or terminating active force production, thereby adjusting the Frank-Starling mechanism of the heart. Therefore, titin is a self-adjustable and multi-functional spring that is indispensable for proper heart functions. Here, we discuss how titin regulates the passive and active properties of cardiac muscle in normal physiological conditions as well as in chronic heart disease.

    Original languageEnglish
    Pages (from-to)876-881
    Number of pages6
    JournalJournal of Molecular and Cellular Cardiology
    Volume48
    Issue number5
    DOIs
    Publication statusPublished - 2010 May

    Fingerprint

    Connectin
    Myocardium
    Heart Diseases
    Starlings
    Sarcomeres
    Myofibrils
    Cyclic AMP-Dependent Protein Kinases
    Mammals
    Protein Isoforms
    Skeletal Muscle
    Chronic Disease
    Technology

    Keywords

    • Ca
    • Connectin
    • Myocardium
    • Sarcomere

    ASJC Scopus subject areas

    • Molecular Biology
    • Cardiology and Cardiovascular Medicine

    Cite this

    Titin-based regulations of diastolic and systolic functions of mammalian cardiac muscle. / Fukuda, Norio; Terui, Takako; Ishiwata, Shin'ichi; Kurihara, Satoshi.

    In: Journal of Molecular and Cellular Cardiology, Vol. 48, No. 5, 05.2010, p. 876-881.

    Research output: Contribution to journalArticle

    Fukuda, Norio ; Terui, Takako ; Ishiwata, Shin'ichi ; Kurihara, Satoshi. / Titin-based regulations of diastolic and systolic functions of mammalian cardiac muscle. In: Journal of Molecular and Cellular Cardiology. 2010 ; Vol. 48, No. 5. pp. 876-881.
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