MOLECULAR EVOLUTION OF SKELETAL MUSCLE E-C COUPLING

我们一直在从系统发育的角度研究骨骼肌兴奋-收缩偶联的分子机制。骨骼肌E-C偶联的特征是由T管膜上的电荷运动直接触发细胞内钙离子从肌浆网释放，因此E-C偶联不需要外部钙离子的内流。(1)在只缺乏骨骼肌E-C偶联的肌肉发育不全突变小鼠中。在它们的骨骼肌细胞中，硝苯地平特异性固定的电荷成分(Q_&lt；Delta&gt；)不存在，而在正常小鼠的骨骼肌细胞中存在。(2)在无脊椎动物的快速抽动肌肉中，E-C偶联绝对需要外部钙离子的内流。因此，我们认为，在动物进化过程中，获得骨骼肌型E-C偶联的进化发生在某个地方。我们发现，进化的步骤发生在头孢菌素和阿纳坦(早期的…)之间更多的脊椎动物)。这一进化过程伴随着Q&lt；Delta和Gt；的出现。(3)前脊椎动物的横纹肌存在着许多结构变异，以期未来获得新的E-C偶联。在卡氏箭虫中，虽然T管和SR都存在，但咖啡因或兰尼定对细胞内钙离子的释放没有影响。在附节类中，T-小管和SR均存在，咖啡因诱导和兰诺定阻断SR释放Ca~(2+)，而Co~(2+)阻断E-C偶联，表明Ga~(2+)和SR的内流是必需的。在海燕草目动物中，T小管和SR都不存在，因此咖啡因或兰诺定不起作用。在文昌鱼、文昌鱼和文昌鱼中，只存在SR而不存在T管，咖啡因、兰诺定和Co^&lt；2+&gt；24有其特定的作用。在这些动物中，细胞内Ca~(2+)和Gt~(2+)的调节机制有一个逐步演变的过程。(4)我们发现获得电压传感器的分子进化可能在胎鼠骨骼肌发生的早期重复。(5)我们将MDG细胞系引入日本，并建立了检测DHP受体亚型表达的体系。较少

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 … More 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