MECHANISMS OF TRANSMITTER SECRETION AT SYMPATHETIC NERVE VARICOSITIES

由于我们已经引入了解决这个问题的新技术，现在可以将交感神经末梢上称为静脉曲张的释放部位分泌递质量子包的机制带到分子水平。这个问题有两个主要方面。第一个问题涉及到蛋白质如何参与控制调节分泌或胞吐的量子包的发射执行这一功能。这些蛋白质（突触融合蛋白、小突触泡蛋白、SNAP 25和突触结合蛋白）与钙通道一起与停靠的突触囊泡复合，所述突触囊泡含有适当地称为分泌体的分泌模块中的递质量子。这里的主要问题是确定是否只有一个分泌体参与神经冲动到达时的递质释放，静脉曲张中这些分泌体的数量是否决定了其分泌量子的概率，以及从根本上说，当有足够的钙离子通过分泌体相关的钙通道流入冲动时，分泌体内的蛋白质如何合作触发胞吐作用。另一个问题涉及钙从静脉曲张中去除的机制，一旦它通过通道进入，这种钙可以对分泌体参与随后冲动分泌的程度产生相当大的影响。此外，这种钙的流入可以通过由第一脉冲释放的递质来调节随后的脉冲。目前的研究将解决这些问题，提供一个单一的交感神经静脉曲张分泌的分子描述。

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.