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¹ Department of Cell Physiology, The Jikei University School of Medicine, Tokyo 105-8461, Japan
² Laboratory of Marine Biotechnology and Microbiology, Hokkaido University, Hakodate 041-8611, Japan
³ Department of Physics, Waseda University, Tokyo 169-8555, Japan

Correspondence to Norio Fukuda: noriof{at}jikei.ac.jp

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 Ca²⁺-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 Ca²⁺ 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.

J. O-Uchi's present address is Aab Cardiovascular Research Institute, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14642.

Abbreviations used in this paper: BDM, 2,3-butanedione monoxime; cTn, cardiac troponin complex; cTnI, cardiac troponin I; MyBP-C, myosin-binding protein C; n_H, Hill coefficient; PCRF, hybrid troponin complex (fast skeletal troponin T with cardiac troponin I and C); PKI, PKA inhibitor; PLV, porcine left ventricular; PP1, protein phosphatase 1; RP, rabbit psoas; SL, sarcomere length; sTn, fast skeletal troponin complex; sTnT, fast skeletal troponin T; Tm, tropomyosin; Tn, troponin.

© 2009 Matsuba et al.
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				D. Matsuba, T. Terui, J. O-Uchi, H. Tanaka, T. Ojima, I. Ohtsuki, S. Ishiwata, S. Kurihara, and N. Fukuda Protein kinase A-dependent modulation of Ca2+ sensitivity in cardiac and fast skeletal muscles after reconstitution with cardiac troponin J. Cell Biol., June 1, 2009; 185(5): i12 - i12. [Full Text]

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