MECHANISMS OF TRANSMITTER SECRETION AT SYMPATHETIC NERVE VARICOSITIES

交感神经静脉曲张的递质分泌机制

• 批准号: nhmrc : 107212
• 负责人: Prof Maxwell Bennett
• 金额: $ 29.25万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/mechanisms-transmitter-secretion-nerve-varicosities/81266
• 关键词: MECHANISMS; TRANSMITTER; SECRETION; SYMPATHETIC; NERVE

The mechanism by which quantal packets of transmitter are secreted from release sites called varicosities on sympathetic nerve terminals can now be taken to the molecular level, given the new techniques which we have introduced to solve this problem. There are two main facets to the problem. The first of these involves the question of how proteins involved in controlling the regulated secretion or exocytosis of the quantal packets of transmitter carry out this function. These proteins (syntaxin, synaptobrevin, SNAP25 and synaptotagmin) together with a calcium channel are complexed with a docked synaptic vesicle containing a quantum of transmitter in a module of secretion appropriately called a secretosome. The leading questions here are to determine if only a single secretosome participates in transmitter release on the arrival of a nerve impulse, whether the number of these secretosomes in a varicosity determines its probability for secretion of a quantum, and fundamentally, how do the proteins within the secretosome cooperate to trigger exocytosis when there is sufficient calcium influx through the secretosome-associated calcium channel following the impulse. The other problem concerns the mechanism of removal of calcium from the varicosity once it has entered through the channels, This calcium can have considerable affects on the extent to which secretosomes participate in secretion with subsequent impulses. Furthermore, this influx of calcium can be modulated for subsequent impulses by transmitter released by the first impulse. The present research will solve these problems, providing a molecular description of secretion from single sympathetic varicosities.

量子信号从交感神经末梢的释放位点（称为静脉曲张）分泌的机制现在可以被带到分子水平，因为我们已经引入了解决这个问题的新技术。这个问题主要有两个方面。第一个问题是，参与控制递质量子包的受调节分泌或胞吐的蛋白质是如何执行这一功能的。这些蛋白（syntaxin, synaptobrevin， SNAP25和synaptotagmin）与钙通道一起与停靠的突触囊泡（在分泌模块中含有一定数量的递质，适当地称为分泌体）结合。这里的主要问题是确定在神经冲动到达时是否只有一个分泌小体参与递质释放，静脉曲张中这些分泌小体的数量是否决定其分泌量的概率，以及从根本上说，当有足够的钙通过分泌小体相关的钙通道流入时，分泌小体内的蛋白质如何协同触发胞外分泌。另一个问题是，一旦钙通过通道进入静脉曲张，钙从静脉曲张中去除的机制。这些钙可以对分泌小体参与随后冲动分泌的程度产生相当大的影响。此外，这种钙的流入可以被第一个脉冲释放的发射机调制为随后的脉冲。目前的研究将解决这些问题，提供单个交感静脉曲张分泌的分子描述。