Troponin and titin coordinately regulate length-dependent activation in skinned porcine ventricular muscle

Takako Terui, Munguntsetseg Sodnomtseren, Douchi Matsuba, Jun Udaka, Shin'Ichi Ishiwata, Iwao Ohtsuki, Satoshi Kurihara, Norio Fukuda

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    Abstract

    We investigated the molecular mechanism by which troponin (Tn) regulates the Frank-Starling mechanism of the heart. Quasi-complete reconstitution of thin filaments with rabbit fast skeletal Tn (sTn) attenuated length-dependent activation in skinned porcine left ventricular muscle, to a magnitude similar to that observed in rabbit fast skeletal muscle. The rate of force redevelopment increased upon sTn reconstitution at submaximal levels, coupled with an increase in Ca2+ sensitivity of force, suggesting the acceleration of cross-bridge formation and, accordingly, a reduction in the fraction of resting cross-bridges that can potentially produce additional active force. An increase in titin-based passive force, induced by manipulating the prehistory of stretch, enhanced length-dependent activation, in both control and sTn-reconstituted muscles. Furthermore, reconstitution of rabbit fast skeletal muscle with porcine left ventricular Tn enhanced length-dependent activation, accompanied by a decrease in Ca2+ sensitivity of force. These findings demonstrate that Tn plays an important role in the Frank-Starling mechanism of the heart via on-off switching of the thin filament state, in concert with titin-based regulation.

    Original languageEnglish
    Pages (from-to)275-283
    Number of pages9
    JournalJournal of General Physiology
    Volume131
    Issue number3
    DOIs
    Publication statusPublished - 2008 Mar

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    ASJC Scopus subject areas

    • Physiology

    Cite this

    Terui, T., Sodnomtseren, M., Matsuba, D., Udaka, J., Ishiwata, SI., Ohtsuki, I., Kurihara, S., & Fukuda, N. (2008). Troponin and titin coordinately regulate length-dependent activation in skinned porcine ventricular muscle. Journal of General Physiology, 131(3), 275-283. https://doi.org/10.1085/jgp.200709895