| Project/Area Number |
06044163
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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 |
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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) |
CHRACHRI Abdesslam Research Fellow, Marine Biological Association of UK, 研究員
WILLIAMSON Roddy Advanced Research Fellow, Marine Biological Association of UK, 上級研究員
BROWN Euan r Advanced Research Fellow, Marine Biological Association of UK, 上級研究員
BONE Quentin Research Director, Marine Biological Association of UK, 部長
KUKITA Fumio Research Associate, National Institute for Physiological Sciences, 生体膜, 助手 (40113427)
TSUTSUI Izuo Research Associate, National Institute for Physiological Sciences, 生体膜, 助手 (80202183)
YAMAGISHI Shunnichi Professor, National Institute for Physiological Sciences, 生体膜, 教授 (70014032)
ABBOTT N.Joa ロンドン大学キングス校, 副教授
BROWN R.Euan プリムス海洋生物研究所, 研究員
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 1995: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1994: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Skeletal muscle / E-C coupling / Calcium ion / Evolution / DHP-receptor / Cephalochordate / Agnathan / Nifedipine / Nerve |
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| Research Abstract |
A distinctive feature of the excitation-contraction coupling (E-C coupling) of skeletal muscle in higher vertebrates in that Ca^<2+> -influx is not necessary for contraction. This is because membrane depolarisation directly triggers Ca^<2+> release from the sarcoplasmic reticulum (SR). The molecule responsible for this signal transduction in the transverse tubular (T-tubular) membrane is a dihydropyridine (DHP) receptor, which is thought to be responsible for the dual function, of voltage sensor (underlying E-C coupling) and the L-type Ca^<2+> channel. In E-C coupling in invertebrate muscle fibers, influx of external Ca^<2+> is necessary for contraction, and a DHP -receptor is present, but responsible for only the L-type Ca^<2+> channel function. Therefore, the E-C coupling mechanism in higher vertebrates is qualitativele different from that in invertebrates. There must have been an evolutionary step to acquire the novel depolarisation-induced Ca^<2+> release mechanism. The main object
… More
ive of the present research project is to examine species representing different stages in animal evolution, and compare the biophysical and morphological properties of E-C coupling.
We reported that the evolutionry step might have occurred in lower chordates between amphioxus (Branchiostoma lanceolatum) and lamprey (Lampetra planeri). Whole-cell voltage clamp experiments on single fast muscle fibers suggest that this evolutionary change is accompanied by the appearance of a component of intramembrane charge movement, which is blocked by nifedipine, a DHP derivative, and by a remarkable slowing-down of the activation kinetics of the Ca^<2+> channel. In the fibers of lamprey, mouse, and dogfish, intracellular Ca^<2+>-release (measured using the Ca^<2+> sensitive flurescence dye fluo3) is associated with membrane depolarisation, is resistant to externally applied Co^<2+>, and is suppressed by nifedipine. In contrast, in the amphioxus fiber, Ca^<2+>-release is suppressed by Co^<2+>. The results strongly support the hypothesis that nifedipine-sensitive intramembrane charge movement is the signal tansduction mechanism of vertebrate skeletal muscle E-C coupling.
Marine invertebrates and lower vertebrates represent a unique 'gene-bank' of such diverse material and should provide us with chronological evidence about the molecular evolution of the DHP-receptor. Less
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