Molecular mechanism of length-dependent activation in cardiac muscle
| 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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Report
(3 results)
Research Products
(50 results)
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[Journal Article] Disuse-induced preferential loss of the giant protein titin depresses muscle performance via abnormal sarcomeric organization2008
Author(s)
Udaka, J., Ohmori, S., Terui, T., Ohtsuki, I., Ishiwata, S., Kurihara, S., Fukuda, N
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Journal Title
Journal of General Physiology 131
Pages: 33-41
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Troponin and titin coordinately regulate length-dependent activation in skinned porcine ventricular muscle2008
Author(s)
Terui, T., Sodnomtseren, M., Matsuba, D., Udaka, J., Ishiwata, S., Ohtsuki, I., Kurihara, S., Fukuda, N
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Journal Title
Journal of General Physiology 131
Pages: 275-283
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effect of Troponin exchange on length-dependent activation in skinned porcine ventricular muscle.2008
Author(s)
Terui, T., Sodnomtseren, M., Matsuba, D., Udaka, J., Ishiwata, S., Ohtsuki, I, Kurihara, S., Fukuda, N
Organizer
52nd Biophysical Society Annual Meeting
Place of Presentation
Long Beach USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Protein kinase A decreases Ca(2+) sensitivity of force in skeletal muscle after reconstitution with cardiac troponin2008
Author(s)
Matsuba, D., Tanaka, H^<1)>., Terui, T., Ojima, T^<1)>., Ohtsuki, I., Ishiwata, S^<2)>., Kurihara, S., Fukuda, N
Organizer
52nd Biophysical Society Annual Meeting
Place of Presentation
Long Beach USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Troponin regulates length-dependent activation in skinned porcine ventricular muscle2008
Author(s)
Terui, T., Sodnomtseren, M., Ishiwata, S., Ohtsuki, I., Fukuda, N., Kurihara, S
Organizer
The Physiological Society of Japan the 85th Annual Meeting
Place of Presentation
Tokyo Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Disuse-induced changes in Ca^<2+> sensitivity of force in skeletal muscle2007
Author(s)
Udaka, J., Terui, T., Ohmori, S., Ohtsuki, I., Ishiwata, S., Kurihara, S., Fukuda, N
Organizer
51st Biophysical Society Annual Meeting
Place of Presentation
Baltimore USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Disuse-induced changes in length dependence of activation and sarcomere protein expression in skeletal muscle2007
Author(s)
Udaka, J., Terui, T., Ohmori, S., Ohtsuki, I., Ishiwata, S., Kurihara, S., Fukuda, N
Organizer
51st Biophysical Society Annual Meeting
Place of Presentation
Baltimore USA
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Disuse-induced changes in length-dependence of activation in rat soleus muscle2007
Author(s)
Udaka, J., Terui, T., Ohmori, S., Ishiwata, S., Ohtsuki, I., Fukuda, N., Kurihara, S
Organizer
The Physiological Society of Japan the 84th Annual Meeting
Place of Presentation
Osaka Japan
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Disuse-induced changes in Ca^<2+> sensitivity of force in rat soleus muscle2007
Author(s)
Udaka, J., Ohmori, S., Terui, T., Yamaguchi, M., Ishiwata, S., Ohtsuki, I., Fukuda, N., Kurihara, S
Organizer
The Physiological Society of Japan the 84th Annual Meeting
Place of Presentation
Osaka Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] SPOC in a single Cardiomyocyte2007
Author(s)
Serizawa, T., O-Uchi, J., Fukuda, N., Kurihara, S., Ishiwata, S
Organizer
The Biophysical Society of Japan the 45th Annual Meeting
Place of Presentation
Yokohama Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Single soleus muscle fiber function after hindlimb immobilization in rats2006
Author(s)
Udaka, J., Ohmori, S., Ishiwata, S., Ohtsuki, I., Kurihara, S., Fukuda, N
Organizer
6th congress of the federation of Asian and Oceaninan, Physiological Societies
Place of Presentation
Seoul Korea
Description
「研究成果報告書概要(欧文)」より
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