EXCITATION-CONTRACTION COUPLING IN SKELETAL MUSCLE

一种化学传播机制，包括 三磷酸肌醇（InsP 3）作为第二信使， 负责骨骼肌的兴奋-收缩偶联 将在生理/生化实验中进行研究。 的 诱导的磷酸肌醇衍生的肌醇磷酸的释放 骨骼肌的电激活将通过 对从以下物质中获得的代谢成分进行生物化学分析 快速冻结的肌肉 InsP 3和其他肌醇 磷酸盐（环InsP 3），以快速诱导从 肌浆网（SR）将使用光学 技术在皮肤骨骼肌纤维。 的调制 还将研究几种代理的这种能力。 小说 快速释放Ca 2+和磷酸肌醇的技术 （使用光释放衍生物）将被开发， 研究SR对推定激动剂的动力学反应。 这些研究将提供重要的动力学信息， Ca 2+释放生理过程的化学调节 它们将补充我们关于 E-C耦合中的传输延迟。 Na和K的作用 T-小管去极化和可能的离子电导 耗尽/积累现象将借助 电位染料 电压依赖的可能性 磷脂酶C活性内源性存在于T小管中 将在体外直接测试膜。 藤壶研究 肌肉纤维将使我们能够评估肌醇的作用 磷酸盐对无脊椎动物肌肉的E-C耦合， 提供了深入了解细胞外钙的作用， 规范这个过程。

The possibility that a chemical transmission mechanism, involving inositol (1,4,5) trisphosphate (InsP3) as a second messenger, is responsible for excitation-contraction coupling in skeletal muscle will be studied in physiological/biochemical experiments. The release of phosphoinositide-derived inositol phosphates induced by the electrical activation of skeletal muscle will be studied by the biochemical analysis of metabolic constituents obtained from rapidly frozen muscles. The ability of InsP3 and other inositol phosphates (cyclic InsP3) to rapidly induce release from the sarcoplasmic reticulum (SR) will be assessed using optical techniques in skinned skeletal muscle fibers. The modulation of this ability by several agents will also be investigated. Novel techniques to produce rapid release of Ca2+ and inositol phosphates (using photoreleasable derivatives) will be developed in order to investigate the kinetic response of the SR to putative agonists. These studies will give important kinetic information on the chemical modulation of the physiological process of Ca2+ release and they will complement our new findings about the nature of the transmission delay in E-C coupling. The role of Na and K conductances in the T-tubule depolarization and in possible ion depletion/accumulation phenomena will be studied with the aid of potentiometric dyes. The possibility that voltage dependent phospholipase C activity is endogenously present in the T tubule membranes will be directly tested in vitro. Studies in barnacle muscle fibers will allow us to evaluate the role of inositol phosphates on the E-C coupling of invertebrate muscle and will provide insights into the role of extracellular Ca in the regulation of this process.