Intracellular calcium dependence of transmitter release rates at a fast central synapse
Intracellular calcium dependence of transmitter release rates at a fast central synapse
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DOI：
10.1038/35022702
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发表时间：
2000-08-24
期刊：
影响因子：
64.8
通讯作者：
Neher, E
中科院分区：
文献类型：
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作者：
Schneggenburger, R;Neher, E
钙离子触发的突触小泡融合和神经递质释放是中枢神经系统中的基本信号步骤。一般认为，快速递质释放是由囊泡融合部位(1-5)附近细胞内钙离子浓度([Ca~(2+)](I))升高到至少100微米触发的。然而，对于中枢神经系统中的突触，没有对这种局部[Ca~(2+)](I)信号的实验估计。在这里，我们通过在Hold的花萼的大型突触终末使用钙离子去势，发现阶梯式升高到只有10亩M[Ca~(2+)](I)诱导快速递质释放，在不到3ms的时间内耗尽大约80%的可用小泡池。[Ca~(2+)](I)步骤后递质释放速率的动力学分析揭示了钙结合和囊泡融合的速率常数。这些结果表明，在单个突触前动作电位中，局部瞬间(约0.5ms)[Ca~(2+)](I)升高至峰值低至25微米，可以解释递质的释放。用于囊泡融合的钙传感器在正常释放概率下远未达到饱和。这种非饱和性，以及触发囊泡融合的高细胞内钙协同作用，使得快速突触传递对局部[Ca~(2+)](I)的变化非常敏感。
Calcium-triggered fusion of synaptic vesicles and neurotransmitter release are fundamental signalling steps in the central nervous system. It is generally assumed that fast transmitter release is triggered by elevations in intracellular calcium concentration ([Ca2+](i)) to at least 100 mu M near the sites of vesicle fusion(1-5). For synapses in the central nervous system, however, there are no experimental estimates of this local [Ca2+](i) signal. Here we show, by using calcium ion uncaging in the large synaptic terminals of the calyx of Held, that step-like elevations to only 10 mu M [Ca2+](i) induce fast transmitter release, which depletes around 80% of a pool of available vesicles in less than 3 ms. Kinetic analysis of transmitter release rates after [Ca2+](i) steps revealed the rate constants for calcium binding and vesicle fusion. These show that transient (around 0.5 ms) local elevations of [Ca2+](i) to peak values as low as 25 mu M can account for transmitter release during single presynaptic action potentials. The calcium sensors for vesicle fusion are far from saturation at normal release probability. This non-saturation, and the high intracellular calcium cooperativity in triggering vesicle fusion, make fast synaptic transmission very sensitive to modulation by changes in local [Ca2+](i).