Parnas Hanna, Parnas Itzchack
Department of Neurobiology, The Life Science Institute, The Hebrew University of Jerusalem, Edmond J. Safra campus, Jerusalem 91904, Israel.
Trends Neurosci. 2007 Feb;30(2):54-61. doi: 10.1016/j.tins.2006.12.001. Epub 2006 Dec 13.
It is widely believed that the initiation of transmitter release in fast synapses is triggered by rapid Ca2+ entry and that the termination of release is governed by removal of Ca2+ from below the release sites. We argue that, although Ca2+ is essential for release, fast-entry kinetics render Ca2+ incapable of being the limiting factor for the initiation of release, and the relatively slow removal of Ca2+ cannot be the limiting factor for the termination of release. We suggest, and provide supporting evidence for, a novel general mechanism for control of fast transmitter release (in the range of milliseconds) from nerve terminals. According to this mechanism, two factors control release: Ca2+ and voltage-sensitive presynaptic inhibitory G-protein-coupled receptors (GPCRs). Inhibitory autoreceptors are known to mediate slow feedback inhibition of transmitter release. We discuss the evidence showing that these receptors also control the initiation and termination of transmitter release by directly interacting with core proteins in the exocytotic machinery. This novel mechanism has important implications for understanding the regulation of transmitter release, synaptic plasticity and neuronal circuit properties.
人们普遍认为，快速突触中递质释放的起始是由Ca2+的快速内流触发的，而释放的终止则取决于从释放位点下方清除Ca2+。我们认为，尽管Ca2+对释放至关重要，但快速内流动力学使Ca2+无法成为释放起始的限制因素，并且Ca2+相对缓慢的清除也不能成为释放终止的限制因素。我们提出并提供了支持证据，证明了一种控制神经末梢快速递质释放（在毫秒范围内）的新的一般机制。根据这一机制，有两个因素控制释放：Ca2+和电压敏感的突触前抑制性G蛋白偶联受体（GPCR）。已知抑制性自身受体介导递质释放的缓慢反馈抑制。我们讨论了证据，表明这些受体还通过与胞吐机制中的核心蛋白直接相互作用来控制递质释放的起始和终止。这种新机制对于理解递质释放的调节、突触可塑性和神经元回路特性具有重要意义。
