The inositol high-polyphosphate series blocks synaptic transmission by preventing vesicular fusion: a squid giant synapse study.
The inositol high-polyphosphate series blocks synaptic transmission by preventing vesicular fusion: a squid giant synapse study.
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DOI：
10.1073/pnas.91.26.12990
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发表时间：
1994-12
影响因子：
11.1
通讯作者：
R. Llinás;M. Sugimori;E. Lang;M. Morita;M. Fukuda;M. Niinobe;K. Mikoshiba
中科院分区：
文献类型：
--
作者：
R. Llinás;M. Sugimori;E. Lang;M. Morita;M. Fukuda;M. Niinobe;K. Mikoshiba
突触前注射肌醇1，3，4，5-四磷酸，肌醇1，3，4，5，6-pentakisphosphate，或肌醇1，2，3，4，5，6-hexakisphosphate--我们在这里表示肌醇高聚磷酸系列（IHPS）-被证明可以阻断突触传递时，注射到鱿鱼巨突触的前末端。注射1，4，5-三磷酸肌醇不会产生这种效果。突触阻滞的特征在于15-45分钟的时间过程，这取决于前终末纤维中的注射部位;当在终末释放部位进行注射时，发生最快的阻滞。突触前电压钳在发射器释放表明，IHPS块没有修改突触前向内，钙电流。对突触后轴突的突触噪声分析表明，诱发和自发递质释放均被IHPS阻断。强直刺激的突触前纤维在100 Hz的频率表明，块伴随着逐渐减少的突触后反应，表明该块干扰囊泡融合，而不是与囊泡对接。这些结果与最近证实的IHPS结合突触结合蛋白中的C2B结构域的观察结果相结合[Mrsada，M.，Aruga，J.，Niinobe，M.，Aimoto，S. & Mikoshiba，K.（1994）J.Biol.Chem.269，29206-29211]，表明IHPS元件参与囊泡融合和胞吐作用。此外，提出了一个方案，其中synaptotagmin触发发射器释放直接促进突触囊泡与突触前质膜的融合，在协议中的化学突触中的发射器释放的非常快速的性质。
Presynaptic injection of inositol 1,3,4,5-tetraphosphate, inositol 1,3,4,5,6-pentakisphosphate, or inositol 1,2,3,4,5,6-hexakisphosphate--which we denote here the inositol high-polyphosphate series (IHPS)--is shown to block synaptic transmission when injected into the preterminal of the squid giant synapse. This effect is not produced by injection of inositol 1,4,5-trisphosphate. The synaptic block is characterized by a time course in the order of 15-45 min, depending on the injection site in the preterminal fiber; the fastest block occurs when the injection is made at the terminal release site. Presynaptic voltage clamp during transmitter release demonstrates that IHPS block did not modify the presynaptic inward, calcium current. Analysis of synaptic noise at the postsynaptic axon shows that both the evoked and spontaneous transmitter release are blocked by the IHPS. Tetanic stimulation of the presynaptic fiber at frequencies of 100 Hz indicates that block is accompanied by gradual reduction of the postsynaptic response, demonstrating that the block interferes with vesicular fusion rather than with vesicular docking. These results, in combination with the recently demonstrated observation that the IHPS bind the C2B domain in synaptotagmin [Fukada, M., Aruga, J., Niinobe, M., Aimoto, S. & Mikoshiba, K. (1994) J. Biol. Chem. 269, 29206-29211], suggest that IHPS elements are involved in vesicle fusion and exocytosis. In addition, a scheme is proposed in which synaptotagmin triggers transmitter release directly by promoting the fusion of synaptic vesicles with the presynaptic plasmalemma, in agreement with the very rapid nature of transmitter release in chemical synapses.