| Project/Area Number |
12670067
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
UMAZUMME Yoshiki The Jikei University, Physiology, Professor, 医学部, 教授 (40056990)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Maki Jikei University, Physiology, Assistant, 医学部, 助手 (30271315)
TAKEMORI Shigeru The Jikei University, Physiology, Lecturer, 医学部, 講師 (20179675)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Muscle Fatigue / Activation Process / Phosphate Analog |
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| Research Abstract |
To investigate the modulated process of activation causing tension development during muscle fatigue, we separated the activation process by using phosphate analogs ( aluminofluoride, orthvanadate) into three parts; thin filament activation by Ca2+ binding, activation by pre power stroke cross bridges and activation by post power stroke cross bridges. We examine the kinetics of phosphate analogs, and investigate the effect of substances inducing.muscle fatigue (BDM and ADP) on the kinetics of phosphate analogs. Furthermore, to separate the third part of activation process, we simulate the dynamics of myosin ATP binding site with molecular dynamics and measure the course of aluminofluoride release from muscle fiber with 19F-NMR during formation of cross bridges.
1. Recovery of contractility and stiffness: (1). Aluminofluoride was taken in myosin head of 85%. (2). Under the condition of free ATP, activation of thin filament by Ca^<2+> binding. accelerates the release rate of aluminofluoride. (3). Formation of contractile cross-bridge accelerates the release of aluminofluoride. (Yamaguchi ＆ Takemori, 2001) The effect of BDM is that the acceleration of aluminofluoride release was decreased, though that of ADP is that effect on the acceleration does not observe.
2. X-ray diffraction: In the sarcoinere lattice, vanadate binded myosin head is in the similar molecular form to that of M ADP Pi.
3. 19F-NMR: To retain uniformity of sample, minute samples were used. By using nano probe, the signals of aluminofluoride taken in muscle fiber can be measured.
4. Molecular dynamics: On the occasion of cross bridge binding, the behaviors of water molecules in the vicinity of myosin ATP hydrolysis site was simulated with molecular dynamics calculation. The measurements with H NMR of muscle fiber present different results. We are reviewing the difference.
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