| Project/Area Number |
02404044
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
TADA Michihiko Osaka University School of Medicine, Department of Pathophysiology, Professor, 医学部, 教授 (90093434)
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| Co-Investigator(Kenkyū-buntansha) |
INUI Makoto Osaka University School of Medicine, Department of Neurochemistry and Neuropharm, 医学部, 助手 (70223237)
HOSHIDA Shiro Osaka University School of Medicine, First Department of Medicine, Assistant Pro, 医学部, 助手 (80238732)
KUZUYA Tsunehiko Osaka University School of Medicine, Department of Pathophysiology, Associate Pr, 医学部, 助教授 (80150340)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥22,600,000 (Direct Cost: ¥22,600,000)
Fiscal Year 1991: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1990: ¥17,200,000 (Direct Cost: ¥17,200,000)
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| Keywords | Isolated Cardiomycyte / Intracelluar Ca^<2+> Content Measuring System / cardiac SR / Intracellular Ca Transient / phospholamban / Synthetic Peptide / Ca^<2+> Pump ATPase / Monoclonal Antibody |
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| Research Abstract |
We investigated the molecular mechanism of regulation of the proteins of cardiac sarcoplasinic reticulum (SR) which has pivotal role in excitation-contraction coupling of myocardium.
1. Physiological roles of Ca signaling in regulation of cardiac property : We investigated the effects of a monoclonal antibody against phospholamban, one of the Ca signaling proteins in cardiac SR, on ATPase activity of cardiac SR Ca pump ATPase. We found that the antibody inhibit the direct protein-protein interaction between the two SR proteins (J. Mol. Cell. Cardiol. 23, 1223, 1991). We investigated the effects of synthetic phospholamban peptides on the ATPase. The dual regulatory effects of pliospholainban on Ca pump ATPase were revealed ; the cytoplasmic domain for V_<max> and the intramembrane domain for K_<Ca> (J. Biol. Chem. 267, 1647, 1992).
2. Pathological roles of Ca regulatory system of cardiac SR in normal and stressed inyocytes : We established the intracellular Ca^<2+> content measuring system in isolated cardiac myocyte, and evaluated intracellular Ca^<2+> transients of cardiac myocyte under hypoxia and Ca overload. Currently, we are on the way to evaluate the effect of anti-phospholamban monoclonal antibody and the synthetic peptides on the Ca^<2+> transient. We are examining the regulation of the expression of cardiac SR Ca signaling proteins in normal, stressed, or cardioinyopatliic cardiomyocyte.
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