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）：最近的工作表明，在神经元制剂中可以看到高度局部的Ca2+释放事件，例如CA2+肌肉火花。在神经型物理末端，这些Ca2+释放事件似乎是从ryanodine敏感的细胞内Ca2+池散发出来的，而去极化刺激会导致其频率增加。尽管有所有这些信息，但释放的Ca2+的来源以及该现象的生理作用尚不清楚。初步证据表明，这些CA2+释放事件可以代表来自水泡存储的Ca2+的动员。如果是这样，则在胞吞作用的精确位置中的局部Ca2+释放必须调节释放。我的目标是确定这些ryanodine敏感的Ca2+释放事件在神经型物理末端的源，并表明这种动员Ca2+调节了神经肽的分泌。该项目的目的是增加当前对神经型末端生理学的知识，并为CMS中粒状融合发生的机制提供更完整的理解。这些知识可能对理解和治疗突触病理（例如伊顿 - 兰伯特综合征和肌萎缩性侧面硬化症）很重要。