Neurosecretory Granular Ca2+ Release Affects Exocytosis

神经分泌颗粒 Ca2 释放影响胞吐作用

• 批准号: 7056933
• 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/7056933
• 关键词: calcium channel; calcium flux; calcium indicator; calcium ion; dielectric property; electrical conductance; exocytosis; fluorescence spectrometry; granule; immunocytochemistry; inhibitor /antagonist; laboratory mouse; membrane potentials; neuroendocrine system; neurohypophyseal hormone; neurohypophysis; neuropeptides; predoctoral investigator; protein localization; ryanodine; secretion; stimulant /agonist; tissue /cell preparation; vesicle /vacuole

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）：最近的研究表明，在神经元制备物中可以看到高度局部化的Ca 2+释放事件，如肌肉的Ca 2+火花。在神经垂体末梢，这些Ca 2+释放事件似乎是从ryanodine敏感的细胞内Ca 2+池发出的，去极化刺激诱导其频率增加。尽管所有这些信息，释放的Ca 2+的来源，以及这种现象的生理作用是未知的。初步证据表明，这些Ca 2+释放事件可能代表动员的Ca 2+从囊泡商店。如果是这样的话，在胞吐作用的精确位置的局部Ca 2+释放必须调节释放。这是我的目标，以确定这些ryanodine敏感的Ca 2+释放事件在神经垂体终端的来源，并表明，这种动员的Ca 2+调节神经肽分泌。该项目旨在增加目前的知识体系的神经垂体终端的生理学，也提供了一个更完整的了解机制，颗粒融合发生在CMS。这些知识对于理解和治疗诸如Eaton-Lambert综合征和肌萎缩侧索硬化症等突触病理学是重要的。