Cardiac thin filament regulation and the Frank-Starling mechanism

Fuyu Kobirumaki-Shimozawa, Takahiro Inoue, Seine A. Shintani, Kotaro Oyama, Takako Terui, Susumu Minamisawa, Shin'ichi Ishiwata, Norio Fukuda

    Research output: Contribution to journalArticle

    41 Citations (Scopus)

    Abstract

    The heart has an intrinsic ability to increase systolic force in response to a rise in ventricular filling (the Frank-Starling law of the heart). It is widely accepted that the length dependence of myocardial activation underlies the Frank-Starling law of the heart. Recent advances in muscle physiology have enabled the identification of the factors involved in length-dependent activation, viz., titin (connectin)-based interfilament lattice spacing reduction and thin filament "on-off" regulation, with the former triggering length-dependent activation and the latter determining the number of myosin molecules recruited to thin filaments. Patients with a failing heart have demonstrated reduced exercise tolerance at least in part via depression of the Frank-Starling mechanism. Recent studies revealed that various mutations occur in the thin filament regulatory proteins, such as troponin, in the ventricular muscle of failing hearts, which consequently alter the Frank-Starling mechanism. In this article, we review the molecular mechanisms of length-dependent activation, and the influence of troponin mutations on the phenomenon.

    Original languageEnglish
    Pages (from-to)221-232
    Number of pages12
    JournalJournal of Physiological Sciences
    Volume64
    Issue number4
    DOIs
    Publication statusPublished - 2014

    Keywords

    • Calcium
    • Cardiac muscle
    • Titin
    • Troponin

    ASJC Scopus subject areas

    • Physiology

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  • Cite this

    Kobirumaki-Shimozawa, F., Inoue, T., Shintani, S. A., Oyama, K., Terui, T., Minamisawa, S., Ishiwata, S., & Fukuda, N. (2014). Cardiac thin filament regulation and the Frank-Starling mechanism. Journal of Physiological Sciences, 64(4), 221-232. https://doi.org/10.1007/s12576-014-0314-y