Neurosecretory Granular Ca2+ Release Affects Exocytosis

神经分泌颗粒 Ca2 释放影响胞吐作用

• 批准号: 7185151
• 负责人: JAMES M MCNALLY
• 金额: $ 2.9万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-06 至 2008-02-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7185151
• 关键词: Affect; Agonist; Amyotrophic Lateral Sclerosis; Calcium; Electric Capacitance; Event; Exocytosis; Fluo-3; Frequencies; Goals; Image; Kinetics; Knowledge; Lambert-Eaton Myasthenic Syndrome; Lipid Bilayers; Localized; Location; Measurement; Membrane; Monitor; Muscle; Neurons; Neuropeptides; Neurosecretory Granule; Pathology; Physiological; Physiology; Preparation; Resolution; Role; Ryanodine; Source; Stimulus; Synapses; Vesicle; Work; fluorescence imaging; immunocytochemistry; receptor; response

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.

描述（由申请人提供）：最近的工作表明，高度局部化的 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+ 释放事件似乎源自兰尼碱敏感的细胞内 Ca2+ 库，去极化刺激会导致其频率增加。尽管有所有这些信息，释放的 Ca2+ 的来源以及这种现象的生理作用尚不清楚。初步证据表明，这些 Ca2+ 释放事件可能代表了 Ca2+ 从囊泡储存中的动员。如果是这样，胞吐作用精确位置的局部 Ca2+ 释放必须调节释放。我的目标是确定神经垂体末梢中这些兰尼碱敏感的 Ca2+ 释放事件的来源，并证明 Ca2+ 的这种动员调节神经肽的分泌。该项目旨在丰富当前神经垂体末梢生理学知识体系，并提供对 CMS 中颗粒融合发生机制的更完整理解。这些知识对于理解和治疗伊顿-兰伯特综合征和肌萎缩侧索硬化症等突触病理学非常重要。