Disuse-induced preferential loss of the giant protein titin depresses muscle performance via abnormal sarcomeric organization

Jun Udaka, Shintaro Ohmori, Takako Terui, Iwao Ohtsuki, Shin'ichi Ishiwata, Satoshi Kurihara, Norio Fukuda

    Research output: Contribution to journalArticle

    64 Citations (Scopus)

    Abstract

    Persistent muscle weakness due to disuse-associated skeletal muscle atrophy limits the quality of life for patients with various diseases and individuals who are confined to bed. Fibers from disused muscle exhibit a marked reduction in active force production, which can exacerbate motor function, coupled with the well-known loss of muscle quantity. Despite recent understanding of the signaling pathways leading to the quantity loss, the molecular mechanisms of the depressed qualitative performance still remain elusive. Here we show that long-term disuse causes preferential loss of the giant sarcomere protein titin, associated with changes in physiologic muscle function. Ca2+ sensitivity of active force decreased following 6 wk of hindlimb immobilization in the soleus muscle of the rat, accompanied by a shift in the length-active force relationship to the shorter length side. Our analyses revealed marked changes in the disused sarcomere, with shortening of thick and thin filaments responsible for altered length dependence and expansion of interfilament lattice spacing leading to a reduction in Ca2+ sensitivity. These results provide a novel view that disuse-induced preferential titin loss results in altered muscle function via abnormal sarcomeric organization.

    Original languageEnglish
    Pages (from-to)33-41
    Number of pages9
    JournalJournal of General Physiology
    Volume131
    Issue number1
    DOIs
    Publication statusPublished - 2008 Jan

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    Connectin
    Organizations
    Muscles
    Sarcomeres
    Skeletal Muscle
    Proteins
    Hindlimb Suspension
    Muscular Atrophy
    Muscle Weakness
    Quality of Life

    ASJC Scopus subject areas

    • Physiology

    Cite this

    Disuse-induced preferential loss of the giant protein titin depresses muscle performance via abnormal sarcomeric organization. / Udaka, Jun; Ohmori, Shintaro; Terui, Takako; Ohtsuki, Iwao; Ishiwata, Shin'ichi; Kurihara, Satoshi; Fukuda, Norio.

    In: Journal of General Physiology, Vol. 131, No. 1, 01.2008, p. 33-41.

    Research output: Contribution to journalArticle

    Udaka, Jun ; Ohmori, Shintaro ; Terui, Takako ; Ohtsuki, Iwao ; Ishiwata, Shin'ichi ; Kurihara, Satoshi ; Fukuda, Norio. / Disuse-induced preferential loss of the giant protein titin depresses muscle performance via abnormal sarcomeric organization. In: Journal of General Physiology. 2008 ; Vol. 131, No. 1. pp. 33-41.
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