Department of Neuroscience and Center for Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260, USA.
Neuroscience. 2011 Jan 13;172:187-95. doi: 10.1016/j.neuroscience.2010.10.002. Epub 2010 Nov 5.
Dynasore was recently developed as a small molecule, selective non-competitive inhibitor of the protein dynamin. This inhibitor has been shown to block dynamin-dependent endocytosis and is now used commonly to study vesicular recycling at synapses. We have measured the effects of dynasore on spontaneous and evoked transmitter release at the frog neuromuscular junction and shown that, in addition to inhibiting endocytosis, dynasore increases the probability of transmitter release. Furthermore, we have shown that dynasore exposure leads to an increase in resting intra-terminal calcium, but this effect does not completely account for the dynasore-mediated increase in the probability of transmitter release. Therefore, in interpreting effects of the dynamin inhibitor dynasore at synapses, one must be alert to potential increases in presynaptic calcium concentration and transmitter release probability.
Dynasore 最近被开发为一种小分子、选择性非竞争性的蛋白 dynamin 抑制剂。该抑制剂已被证明可阻断 dynamin 依赖性内吞作用,目前常用于研究突触中的囊泡再循环。我们已经测量了 dynasore 对青蛙神经肌肉接头处自发和诱发递质释放的影响,结果表明,dynasore 除了抑制内吞作用外,还增加了递质释放的概率。此外,我们还表明,dynasore 暴露会导致末梢内钙离子静息浓度增加,但这种效应并不能完全解释 dynasore 介导的递质释放概率增加。因此,在解释突触中 dynamin 抑制剂 dynasore 的作用时,必须警惕突触前钙离子浓度和递质释放概率的潜在增加。