Joint Research on E-C coupling in Skeletal Muscle Cells
| Project/Area Number |
03044106
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Tokushima University, Institute for Enzyme Research |
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Principal Investigator |
INOUE Isao Associate Professor, Institute for Enzyme Research Tokushima University, 酵素科学研究センター, 助教授 (80001973)
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| Co-Investigator(Kenkyū-buntansha) |
BOURNAUD Roland Professor, Physiologie General, Universite de Paris XII, 理学部, 教授
SHIMAHARA Takeshi Section Chief, Laboratoire de Neurobiologie Cellulaire et Moleculaire, CNRS, 神経分子生物学研究室, 主任研究員
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1992: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1991: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | Skeletal muscle cells / Excitation-contraction coupling / Intramembrane charge movement / Dihydropyridine receptor / Molecular evolution / 興奮ー収縮連関 / DHPリセプタ- / α_1サブユニット / セグメント4 |
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| Research Abstract |
One distinctive feature of the excitation-contraction coupling (E-C coupling) of skeletal muscle in higher vertebrates is Ca^<2+>-influx is not necessary for contraction. This is because membrane depolarization directly triggers Ca^<2+> release from the sarcoplasmic reticulum (SR). The present international joint research was assigned to reveal the signal transduction mechanism in the skeletal muscle transverse tubular membrane underlying the E-C coupling. We used enzymatically dissociated single myotubes form mutant mice with muscular dysgenesis which lack only the skeletal muscle E-C coupling, and found that nifedipine, a dihydropyridine (DHP) derivative had no appreciable effect on the charge movement, whereas in normal myotubes, nifedipine decreased the charge movement by -40% indicting that the charge movement consists of DHP-sensitive and insensitive components. We also explored the genealogical tree of animal evolution, and found that the skeletal muscle E-C coupling appeared in
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lower chordates between amphioxus (Branchiostomalanceolatum) and lamprey (Lampetra planeri). Whole-cell voltage clamp experiments on single fast muscle fibres have revealed that this evolutionary change is accompanied by the appearance of a component of intramembrane charge movement, which is blocked by nifedipine, a dihydropyridine (DHP) derivative. The results reveal that the evolutionary step of the E-C coupling was accompanied by the appearance of DHP-sensitive charge movement, and hence.the DHP-sensitive charge movement expresses the signal transduction process in the DHP-sensitive charge movement expresses the signal transduction process in the DHP-receptor molecule to release Ca^<2+> from the SR in response to membrane depolarization. The present results have also revealed that the DHP-sensitive charge movement is independent of the kinetic properties of the L-type Ca^<2+> channel, although both are thought to be the function of the same DHP-receptor molecule. It becomes now an urgent forthcoming study to analyze the molecular bases of the evolutionary change in E-C coupling, which will make clearer the structural-functional relations of the DHP-receptor molecule. Less
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Report
(2 results)
Research Products
(17 results)
