留美中国学者发表《自然》文章解析神经传递

　　

生物通报道：来自美国国家神经疾病与中风协会（National Institute of Neurological Disorders and Stroke，NINDS）的研究人员针对突触传递过程中突触囊泡融合孔（fusion pore ）开孔过程中出现的问题提出了新的观点，为研究神经突触信号传导提供了重要资料。这一研究成果公布在新鲜出炉的《Nature》杂志上（11月2日）。

文章的通讯作者为NINDS的吴凌刚（Ling-Gang Wu，音译，毕业于上海第二军医大学），第一作者为何立民（Liming He, 音译）。

链接：
Nature 444, 102-105 (2 November 2006) 
doi:10.1038/nature05250; Received 11 May 2006; 
Accepted 14 September 2006; Published online 25 October 2006
Two modes of fusion pore opening revealed by cell-attached recordings at a synapse
[Abstract]

突触是神经元间信息传递的特化结构，在突触前膜中，神经递质贮存在突触囊泡内，并通过胞吐作用释放出来.这个释放神经递质是一个复杂且受到精细调控的过程，涉及多种蛋白质间的相互作用。其中突触囊泡是一类非常小且高度特化的细胞器，它的功能是贮存和释放神经递质。

在释放的过程中，细胞膜融合的这种囊泡会打开一个孔，然后释放神经递质到周质空间，这个孔可以开的比较大，这样囊泡就很快完全释放，“扁”了下来，或者孔在开放后立即关闭起来，产生“kiss-and-run”（吻了就跑）融合。在神经突触研究中这种融合孔的大小，以及“kiss-and-run”的机制至今尚不清楚，而且这种“kiss-and-run”方式产生快速突触电流的能力仍然倍受质疑。

在这篇文章中，Wu等人记录下了单囊泡融合过程中融合孔的动力学资料，观测了calyx-type突触的完全释放和“kiss-and-run”。对于完全释放，最初的融合孔电导（conductance (G_p)）通常大于375 pS，并且在达到299 pS ms^–1之后迅速增加；而“kiss-and-run”融合则是一个简单的电容闪烁（capacitance flicker (<2 s)）——大部分G_p >288 pS，其余是在15–288 pS范围。由于G_p 比较大的(>288 pS)会很快放电，因此会引起快速的突触电流，而比较小的G_p ，突触电流则产生的比较慢和小。

这些结果都说明“kiss-and-run”确实会在突触中出现，并且可以产生快速的突触后电流（postsynaptic currents），这也就是表明不同的融合孔的大小可以用于调控突触电流的动力学和振幅。（生物通：张迪）

 

 

 

 

 

附：
Ling-Gang Wu, M.D., Ph.D., Investigator


Dr. Wu received his M.D. degree in 1985 from Second Military Medical College, Shanghai. In 1994 he received his Ph.D. in Neuroscience from Baylor College of Medicine, Houston where he worked with Peter Saggau studying the role of presynaptic voltage-dependent calcium channels in controlling transmitter release. From 1994 to 1996, He did postdoctoral training with William J. Betz at University of Colorado Medical School, Denver where he studied the kinetic regulation of endocytosis at frog neuromuscular junctions with FM dye imaging methods. From 1996 to 1999, he did another postdoctoral training with Bert Sakmann in the Max Planck Institute, Heidelberg, Germany, where he identified the calcium channel types and studied the presynaptic mechanisms underlying short-term synaptic depression at a giant nerve terminal, the calyx of Held in rat brainstem. From 1999 to May of 2003, he was an assistant professor in Washington University, St. Louis, where his laboratory applied the capacitance recording technique to study regulation of the kinetics of endocytosis at the calyx of Held. Dr. Wu joined NINDS as an Investigator in June of 2003. His laboratory is using electrophysiological, imaging, biochemical and molecular biological techniques to investigate the cellular and molecular mechanisms underlying generation and regulation of endocytosis and synaptic plasticity at the calyx-type synapse.