| Project/Area Number |
18500321
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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 |
Neurophysiology and muscle physiology
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
FUKUDA Norio Jikei University School of Medicine, Department of Cell Physiology, Assistant Professor (30301534)
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| Co-Investigator(Kenkyū-buntansha) |
KURIHARA Satoshi The Jikei University, Department of Cell Physiology, Professor (90057026)
OHTSUKI Iwao The Jikei University, Department of Cell Physiology, Visiting Professor (70009992)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,930,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Cardiac muscle / Starling's law of the heart / Length-denendent activation / Troponin / Titin / Cross-bridges / Frank-Starling機構 / 静止張力 / 格子間隔 |
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| Research Abstract |
An increase in ventricular volume enhances the systolic performance of the heart ; this is known as the Frank-Starling law of the heart. "The Law" is a manifestation of the sarcomere length dependence of myocardial activation, in which active force is a function of the resting sarcomere length (i.e., length-dependent activation). We have reported that passive force resulting from extension of the giant elastic protein titin (also known as connectin) operates as a triggering factor in this phenomenon. In the present study, we investigated whether or not length-dependent activation is modulated at the thin filament level. Quasi-complete reconstitution of thin filaments with rabbit fast skeletal troponin (sTn) attenuated length-dependent activation in porcine left ventricular muscle to a magnitude similar to that observed in rabbit fast skeletal muscle, accompanied by an increase in Ca^<2+> sensitivity of force. We also found that sTn reconstitution accelerated cross-bridge kinetics at submaximal levels, suggesting that sTn reconstitution results in a decrease in the fraction of recruitable (i.e., resting) cross-bridges that can potentially produce active force. An increase in titin-based passive force, induced by manipulating the pre-history of stretch, enhanced length-dependent activation, with and without sTn reconstitution. Furthermore, reconstitution of rabbit fast skeletal muscle with porcine left ventricular Tn enhanced length-dependent activation, accompanied by a decrease in Ca^<2+> sensitivity of force. These results favor the interpretation that troponin plays an important role in length-dependent activation via on-off switching of the thin filament state, in concert with titin-based regulation.
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