| Co-Investigator(Kenkyū-buntansha) |
BROWN Euan R. MARINE BIOLOGICAL ASSOCIATION OF UK,BBSRC ADVANCED FELLOW, 高等研究員
BONE Quentin MARINE BIOLOGICAL ASSOCIATION OF UK,PROFESSOR EMERITUS, 名誉教授
BOURNAUD Roland UNIVERSITY PARIS XII,PROFESSOR, 生理学, 教授
TSUTSUI Izuo NATIONAL INSTITUTE FOR PHYSIOLOGICAL SCIENCES,RESEARCH ASSOCIATE, 生体膜, 助手 (80202183)
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| Research Abstract |
We have been investigating the molecular mechanisms in skeletal muscle excitation-contraction coupling on the aspect of phylogeny. Skeletal muscle E-C coupling is characterized by direct triggering by charge movement in the T-tubular membrane of intracellular Ca^<2+> release from the sarcoplasmic reticulum, hence influx of external Ca^<2+> is not required in the E-C coupling.
(1)In mutant mice with muscular dysgenesis (MDG) that lack only skeletal muscle E-C coupling. a component of charge (Q_<delta>) which is specifically immobilized by nifedipine is found to be absent in their skeletal muscle cells, whereas it is present in those of normal mice.
(2)In fast twitch muscle of invertebrate, E-C coupling absolutely requires influx of external Ca^<2+>.It is therefore suggested that evolution to acquire skeletal muscle type E-C coupling occurred somewhere during animal evolution. We found that the evolutionary step occurred in adiscrete manner between cephalochordate and agnathan (the earlies
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t vertebrate). This evolutionary step is found to be accompanied by the appearance of Q_<delta>.
(3)There are many structural variations of striated muscle in pre-vertebrates toward the future acquirement of novel E-C coupling. In the cataegnatha, Sagitta, although both T-tubules and SR are present, caffeine or ryanodine has no effect on intracellular Ca^<2+> release. In the appencliculata, Oikopleuxa, both T-tubules and SR are present, caffeine induces and ryanodine blocks Ca^<2+> release from SR but Co^<2+> blocks E-C coupling indicating Ga^<2+> influx is necessary. In the thraliacea, Doliolum, both T-tubules and SR are absent, hence caffeine or ryanodine has no effect. In the cephalochordata, amphioxus, no T-tubUles but SR is present, caffeine, ryanodine, and Co^<2+>24 have their specific effects. In there animals, there is a gradual evolution of regulation mechanisms of intracellular Ca^<2+>.
(4)We found that the molecular evolution to acquire the voltage sensor may be repeated in the early stage of skeletal myogenesis in fetal mice.
(5)We have brought the MDG ell line into Japan, and established the system of examining expression of DHP- receptor subtypes. Less
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