Calcium secretion coupling at calyx of held governed by nonuniform channel-vesicle topography
Calcium secretion coupling at calyx of held governed by nonuniform channel-vesicle topography
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DOI：
10.1523/jneurosci.22-05-01648.2002
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发表时间：
2002-03-01
影响因子：
5.3
通讯作者：
Sakmann, B
中科院分区：
文献类型：
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作者：
Meinrenken, CJ;Borst, JGG;Sakmann, B
哺乳动物中枢神经系统突触的相位递质释放受局部[Ca2+]瞬变调节，这控制了突触前膜活性区（AZs）的易释放囊泡的融合。这些[Ca2+]瞬态的时间过程和振幅关键地决定了释放的时间过程和振幅，从而决定了突触连接的频率和振幅调谐。到目前为止，[Ca2+]瞬态的时空性质以及相对于囊泡的释放控制Ca2+通道的数量和位置，释放位点的“地形”仍然难以捉摸。我们使用时间依赖模型来模拟Ca2+内流，三维缓冲Ca2+扩散，以及Ca2+与释放传感器的结合。模型的参数受最近的花萼解剖和生物物理数据的限制。将模型的预测与先前在各种实验条件下测量的释放概率进行比较，我们推断出哪些释放位点地形可能在花萼上起作用：在每个AZ中，一个或几个Ca2+通道簇控制囊泡的释放。囊泡到簇的距离在单个花萼的多个释放点之间变化（范围从30到300纳米，平均接近100纳米）。假设这种地形，不同位置的囊泡暴露于不同的[Ca2+]瞬态，在动作电位期间峰值振幅范围为0.5至40毫微米（半宽度类似于400毫微米）。因此囊泡具有不同的释放概率，范围从
Phasic transmitter release at synapses in the mammalian CNS is regulated by local [Ca2+] transients, which control the fusion of readily releasable vesicles docked at active zones (AZs) in the presynaptic membrane. The time course and amplitude of these [Ca2+] transients critically determine the time course and amplitude of the release and thus the frequency and amplitude tuning of the synaptic connection. As yet, the spatiotemporal nature of the [Ca2+] transients and the number and location of release-controlling Ca2+ channels relative to the vesicles, the "topography" of the release sites, have remained elusive. We used a time-dependent model to simulate Ca2+ influx, three-dimensional buffered Ca2+ diffusion, and the binding of Ca2+ to the release sensor. The parameters of the model were constrained by recent anatomical and biophysical data of the calyx of Held. Comparing the predictions of the model with previously measured release probabilities under a variety of experimental conditions, we inferred which release site topography is likely to operate at the calyx: At each AZ one or a few clusters of Ca2+ channels control the release of the vesicles. The distance of a vesicle to the cluster(s) varies across the multiple release sites of a single calyx (ranging from 30 to 300 nm; average similar to100 nm). Assuming this topography, vesicles in different locations are exposed to different [Ca2+] transients, with peak amplitudes ranging from 0.5 to 40 muM (half-width similar to400 musec) during an action potential. Consequently the vesicles have different release probabilities ranging from