Protein kinase A-dependent modulation of Ca2+ sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin

Douchi Matsuba, Takako Terui, Jin O-Uchi, Hiroyuki Tanaka, Takao Ojima, Iwao Ohtsuki, Shin'ichi Ishiwata, Satoshi Kurihara, Norio Fukuda

    Research output: Contribution to journalArticle

    16 Citations (Scopus)

    Abstract

    Protein kinase A (PKA)-dependent phosphorylation of troponin (Tn)I represents a major physiological mechanism during β-adrenergic stimulation in myocardium for the reduction of myofibrillar Ca2+ sensitivity via weakening of the interaction with TnC. By taking advantage of thin filament reconstitution, we directly investigated whether or not PKA-dependent phosphorylation of cardiac TnI (cTnI) decreases Ca2+ sensitivity in different types of muscle: cardiac (porcine ventricular) and fast skeletal (rabbit psoas) muscles. PKA enhanced phosphorylation of cTnI at Ser23/24 in skinned cardiac muscle and decreased Ca2+ sensitivity, of which the effects were confirmed after reconstitution with the cardiac Tn complex (cTn) or the hybrid Tn complex (designated as PCRF; fast skeletal TnT with cTnI and cTnC). Reconstitution of cardiac muscle with the fast skeletal Tn complex (sTn) not only increased Ca2+ sensitivity, but also abolished the Ca 2+-desensitizing effect of PKA, supporting the view that the phosphorylation of cTnI, but not that of other myofibrillar proteins, such as myosin-binding protein C, primarily underlies the PKA-induced Ca2+ desensitization in cardiac muscle. Reconstitution of fast skeletal muscle with cTn decreased Ca2+ sensitivity, and PKA further decreased Ca 2+ sensitivity, which was almost completely restored to the original level upon subsequent reconstitution with sTn. The essentially same result was obtained when fast skeletal muscle was reconstituted with PCRF. It is therefore suggested that the PKA-dependent phosphorylation or dephosphorylation of cTnI universally modulates Ca2+ sensitivity associated with cTnC in the striated muscle sarcomere, independent of the TnT isoform.

    Original languageEnglish
    Pages (from-to)571-581
    Number of pages11
    JournalJournal of General Physiology
    Volume133
    Issue number6
    DOIs
    Publication statusPublished - 2009 Jun

    Fingerprint

    Troponin
    Cyclic AMP-Dependent Protein Kinases
    Skeletal Muscle
    Myocardium
    Phosphorylation
    Psoas Muscles
    Sarcomeres
    Troponin I
    Striated Muscle
    Adrenergic Agents
    Protein Isoforms
    Swine
    Rabbits

    ASJC Scopus subject areas

    • Physiology

    Cite this

    Protein kinase A-dependent modulation of Ca2+ sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin. / Matsuba, Douchi; Terui, Takako; O-Uchi, Jin; Tanaka, Hiroyuki; Ojima, Takao; Ohtsuki, Iwao; Ishiwata, Shin'ichi; Kurihara, Satoshi; Fukuda, Norio.

    In: Journal of General Physiology, Vol. 133, No. 6, 06.2009, p. 571-581.

    Research output: Contribution to journalArticle

    Matsuba, D, Terui, T, O-Uchi, J, Tanaka, H, Ojima, T, Ohtsuki, I, Ishiwata, S, Kurihara, S & Fukuda, N 2009, 'Protein kinase A-dependent modulation of Ca2+ sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin', Journal of General Physiology, vol. 133, no. 6, pp. 571-581. https://doi.org/10.1085/jgp.200910206
    Matsuba, Douchi ; Terui, Takako ; O-Uchi, Jin ; Tanaka, Hiroyuki ; Ojima, Takao ; Ohtsuki, Iwao ; Ishiwata, Shin'ichi ; Kurihara, Satoshi ; Fukuda, Norio. / Protein kinase A-dependent modulation of Ca2+ sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin. In: Journal of General Physiology. 2009 ; Vol. 133, No. 6. pp. 571-581.
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    abstract = "Protein kinase A (PKA)-dependent phosphorylation of troponin (Tn)I represents a major physiological mechanism during β-adrenergic stimulation in myocardium for the reduction of myofibrillar Ca2+ sensitivity via weakening of the interaction with TnC. By taking advantage of thin filament reconstitution, we directly investigated whether or not PKA-dependent phosphorylation of cardiac TnI (cTnI) decreases Ca2+ sensitivity in different types of muscle: cardiac (porcine ventricular) and fast skeletal (rabbit psoas) muscles. PKA enhanced phosphorylation of cTnI at Ser23/24 in skinned cardiac muscle and decreased Ca2+ sensitivity, of which the effects were confirmed after reconstitution with the cardiac Tn complex (cTn) or the hybrid Tn complex (designated as PCRF; fast skeletal TnT with cTnI and cTnC). Reconstitution of cardiac muscle with the fast skeletal Tn complex (sTn) not only increased Ca2+ sensitivity, but also abolished the Ca 2+-desensitizing effect of PKA, supporting the view that the phosphorylation of cTnI, but not that of other myofibrillar proteins, such as myosin-binding protein C, primarily underlies the PKA-induced Ca2+ desensitization in cardiac muscle. Reconstitution of fast skeletal muscle with cTn decreased Ca2+ sensitivity, and PKA further decreased Ca 2+ sensitivity, which was almost completely restored to the original level upon subsequent reconstitution with sTn. The essentially same result was obtained when fast skeletal muscle was reconstituted with PCRF. It is therefore suggested that the PKA-dependent phosphorylation or dephosphorylation of cTnI universally modulates Ca2+ sensitivity associated with cTnC in the striated muscle sarcomere, independent of the TnT isoform.",
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    AU - Tanaka, Hiroyuki

    AU - Ojima, Takao

    AU - Ohtsuki, Iwao

    AU - Ishiwata, Shin'ichi

    AU - Kurihara, Satoshi

    AU - Fukuda, Norio

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