MOLECULAR EVOLUTION OF SKELETAL MUSCLE E-C COUPLING

我们从胚胎发生学的角度对骨骼肌兴奋-收缩偶联的分子机制进行了研究。骨骼肌E-C偶联的特点是通过T管膜上的电荷运动直接触发肌浆网释放细胞内Ca^2+，因此E-C偶联不需要外部Ca^2+的内流。(1)In仅缺乏骨骼肌E-C偶联的肌肉发育不全（MDG）突变小鼠。发现<delta>在它们的骨骼肌细胞中不存在被硝苯地平特异性固定的电荷成分（Q_），而在正常小鼠的骨骼肌细胞中存在。(2)In无脊椎动物的快缩肌，E-C偶联绝对需要外部Ca^2+的内流，因此，在动物进化的过程中，骨骼肌型E-C偶联的获得可能发生在某个地方。我们发现，进化步骤发生在头索动物和无颌动物（早期）之间， ...更多信息 t脊椎动物）。这一演化过程伴随着Q_的出现<delta>。（3）前脊椎动物的横纹肌存在着许多结构变异，为将来获得新的E-C偶联奠定了基础。在cataegnatha和Sagitta中，虽然T-小管和SR都存在，但咖啡因或ryanodine对细胞内Ca^2+释放没有影响。在appenciculata，Oikopleuxa，T-小管和SR都存在，咖啡因诱导和ryanodine阻断Ca^&lt;2+&gt;从SR释放，但Co^&lt;2+&gt;阻断E-C耦合，表明Ga^&lt;2+&gt;内流是必要的。在thralialacea中，Doliodine，T-小管和SR都不存在，因此咖啡因或ryanodine没有影响。在头索动物文昌鱼中，无T管但有SR，咖啡因、兰尼碱和Co^2+ 4有其特异性作用。在这些动物中，细胞内Ca^&lt;2+&gt;的调节机制是逐渐进化的。(4)We发现获得电压传感器的分子进化可能在胚胎小鼠骨骼肌发生的早期阶段重复。(5)We已将MDG细胞系引入日本，并建立了检测DHP受体亚型表达的系统。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