Control of Neurohormone Release at Nerve Endings

控制神经末梢的神经激素释放

• 批准号: 9410834
• 负责人: Edward Stuenkel
• 金额: $ 25.63万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9410834&HistoricalAwards=false
• 关键词: Control; Neurohormone; Release; Nerve; Endings

The communication between nerve cells ultimately depends on release of chemical messengers termed neurotransmitters from one nerve cell and subsequent activation of another nerve cell by the released neurotransmitter. Neurotransmitters are released from a specialized portions of a nerve cell called nerve endings or nerve terminals. The most important initiator of neurotransmitter release at nerve terminals is the concentration of free calcium within the terminal. As a consequence of their small size and of their being mixed with glial cells and other nerve cell regions in intact tissue, direct investigation of the basic secretory mechanisms at nerve endings of vertebrates has been limited. It is the purpose of this proposal to utilize a unique nerve terminal preparations of vertebrates which overcomes the above limitations to characterize the fundamental relationships between calcium and induction of secretion of the chemical messengers. State of the art electrophysiological and optical approaches which provide high quantitative and high time resolution will be used in the proposed studies. Specific questions that will be addressed include: What are the qualities of the changes in intracellular calcium that are most important for initiation of secretion? Which calcium entry pathways are most important for induction of the secretory response? Does continued activation by electrical activity alter the importance of these influx pathways? In addition, a number of specific proteins have recently been implicated in the chain of events leading to secretion by biochemical evidence. To date, the specific functions of these proteins have not been elucidated and is a specific aim of this proposal.

神经细胞之间的通信最终取决于从一个神经细胞释放称为神经递质的化学信使，以及随后通过释放的神经递质激活另一个神经细胞。 神经递质是从神经细胞的一个专门部分释放出来的，称为神经末梢或神经末梢。 在神经末梢释放神经递质的最重要的引发剂是末梢内游离钙的浓度。 由于它们体积小，并且在完整组织中与神经胶质细胞和其他神经细胞区域混合，因此对脊椎动物神经末梢的基本分泌机制的直接研究受到限制。 本建议的目的是利用克服上述限制的脊椎动物的独特神经末梢制备物来表征钙与化学信使分泌诱导之间的基本关系。 在拟定研究中将使用最先进的电生理学和光学方法，这些方法可提供高定量和高时间分辨率。 具体的问题，将解决包括：什么是细胞内钙的变化，是最重要的分泌启动的质量？ 哪种钙进入途径对诱导分泌反应最重要？ 电活动的持续激活是否改变了这些流入途径的重要性？ 此外，一些特定的蛋白质最近被牵连的事件链导致分泌的生化证据。 迄今为止，这些蛋白质的具体功能尚未阐明，这是本提案的一个具体目标。