Neurosecretory Granular Ca2+ Release Affects Exocytosis

描述(申请人提供)：最近的研究表明，在神经元准备中可以看到高度局部性的钙释放事件，比如肌肉中的钙火花。在神经垂体终末，这些钙释放事件似乎来自兰尼定敏感的细胞内钙池，去极化刺激引起它们频率的增加。尽管有这些信息，但钙离子释放的来源，以及这一现象的生理作用尚不清楚。初步证据表明，这些Ca~(2+)释放事件可能代表囊泡库中的Ca~(2+)被动员。如果是这样的话，胞吐作用精确位置的局部钙离子释放必须调节释放。我的目标是确定这些兰尼定敏感的钙释放事件的来源，并证明这种钙离子的动员调节神经肽的分泌。这个项目的目的是增加目前关于神经垂体终末生理学的知识体系，并提供对CMS中颗粒融合发生机制的更完整的理解。这些知识可能被证明对理解和治疗突触病理如伊顿-兰伯特综合征和肌萎缩侧索硬化症很重要。

DESCRIPTION (provided by applicant): Recent work has shown that highly localized Ca2+ release events, like Ca2+ sparks of the muscle, can be seen in neuronal preparations. In neurohypophysial terminals, these Ca2+ release events appear to emanate from a ryanodine sensitive intracellular Ca2+ pool, and depolarizing stimuli induces an increase in their frequency. In spite of all this information, the source of the released Ca2+, and a physiological role of this phenomenon is unknown. Preliminary evidence suggests that these Ca2+ release events could represent mobilization of Ca2+ from vesicular stores. If so, localized Ca2+ release in the precise location of exocytosis must modulate release. It is my goal to determine the source of these ryanodine sensitive Ca2+ release events in neurohypophysial terminals, and to show that this mobilization of Ca2+ modulates neuropeptide secretion. This project aims to add to the current body of knowledge of the physiology of the neurohypophysial terminals, and also to provide a more complete understanding of the mechanism by which granular fusion occurs in the CMS. This knowledge could prove to be important for the understanding and treatment of synaptic pathologies such as Eaton-Lambert syndrome, and Amyotrophic lateral sclerosis.