Neurosecretory Granular Ca2+ Release Affects Exocytosis

描述（由申请人提供）：最近的工作表明，高度局部的Ca2+释放事件，如肌肉的Ca2+火花，可以在神经元制剂中看到。在神经垂体末梢，这些Ca2+释放事件似乎来自于对ryanodine敏感的细胞内Ca2+池，去极化刺激诱导其频率增加。尽管有这些信息，Ca2+释放的来源和这一现象的生理作用是未知的。初步证据表明，这些Ca2+释放事件可能代表Ca2+从囊泡储存的动员。如果是这样，在胞吐的精确位置的局部Ca2+释放必须调节释放。我的目标是确定神经垂体末梢这些对ryanodine敏感的Ca2+释放事件的来源，并表明这种Ca2+的动员调节神经肽的分泌。本项目旨在增加对神经垂体末梢生理学的现有知识体系，并提供对CMS中颗粒融合发生的机制的更完整的理解。这些知识对于理解和治疗诸如伊顿-兰伯特综合征和肌萎缩性侧索硬化症等突触病变是非常重要的。

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.