New and corrected simulations of synaptic facilitation
New and corrected simulations of synaptic facilitation
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DOI：
10.1016/s0006-3495(02)73907-6
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发表时间：
2002-09-01
影响因子：
3.4
通讯作者：
Zucker, RS
中科院分区：
文献类型：
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作者：
Matveev, V;Sherman, A;Zucker, RS
Tang 等人 (2000) 证明，在小龙虾的神经肌肉接头处，短期突触促进 (STF) 的积累和衰减特性都受到快速高亲和力 Ca2 缓冲液的强烈影响，表明残留游离 Ca2 在 STF 诱导中的作用。作者提出，实验结果可以用具有两个 Ca2 结合位点的分泌模型来解释，一个介导胞吐作用并位于靠近 Ca2 通道（10-20 nm）的分泌位点，以及一个距离通道较远（80-100 nm）的高亲和力促进位点。在这里，我们报告图 1 和 2 中呈现的数据。原始文章的图 3、C 和 D、6 和 7 显示了 Ca2 扩散方程的数值解，但由于参数值表述错误以及较小程度上的数值算法错误，在质量上是不准确的。因此，唐等人提出的一些结论。关于拟议的模型需要重新审查。在这封信中，我们表明，在适当更改参数值后，模型的大多数预测都成立。也就是说，该模型正确预测了 STF 的强度，以及在快速高亲和力外源 Ca2 缓冲液（例如 Fura-2）存在的情况下 STF 强度的降低及其衰减的加速。如果额外假设内源 Ca2 缓冲液是固定的，那么 STF 的快速（“F1”）和慢速（“F2”）衰减分量也可以成功再现。然而，我们的模拟预测，在 Fura-2 存在的情况下，较慢的 F2 衰变分量将被完全消除，这与 Tang 等人（2000）的实验结果相反（原始论文中的图 3，A 和 B）。我们发现，如果假设突触波顿中的扩散受到限制，那么这一剩余的分歧就可以得到解决，因此 1) 在活动区周围的 200 nm 层中，Fura-2 被固定，并且由于高度弯曲，Ca2+ 的扩散系数降低了五倍； 2) 在终端的其余部分，Fura-2 的扩散系数降低了 100 倍（大概是因为与各种胞质化合物结合）。而且，与唐等人的说法相反。尽管他们的模型无法准确描述 STF 的累积时间过程，但我们表明，我们提出的模型修改导致了 STF 的超线性增长，与实验一致（图 2，A 和 D）。
Tang et al.(2000) demonstrated that, at the crayfish neuromuscular junction, both the accumulation and the decay properties of short-term synaptic facilitation (STF) are strongly affected by the addition of a fast high-affinity Ca2 buffer, suggesting a role of residual free Ca2 in the induction of STF. The authors proposed that the experimental results can be explained by a secretion model with two Ca2 binding sites, a secretory site mediating exocytosis and located close to the Ca2 channel (10–20 nm), and a high-affinity facilitation site located further away (80–100 nm) from the channel. Here we report that the data presented in Figs. 3, C and D, 6, and 7 of the original article, showing numerical solutions to the Ca2 diffusion equations, are qualitatively inaccurate, because of misstated parameter values and, to a lesser extent, numerical algorithm errors. Therefore, some of the conclusions stated by Tang et al. concerning the proposed model require reexamination. In this letter we show that most of the predictions of the model hold, after an appropriate change of parameter values. Namely, the model correctly predicts the magnitude of STF, and the reduction of STF magnitude and acceleration of its decay in the presence of a fast high-affinity exogenous Ca2 buffer, such as Fura-2. The fast (“F1”) and slow (“F2”) decay components of STF are also successfully reproduced, if an additional assumption is made that the endogenous Ca2 buffers are immobile. However, our simulations predict that the slower F2 decay component is completely abolished in the presence of Fura-2, contrary to experimental results of Tang et al.(2000)(Fig. 3, A and B, in the original paper). We found that this remaining disagreement can be resolved if one assumes that the diffusion in the synaptic bouton is restricted, so that 1) in a 200-nm layer around the active zone, Fura-2 is immobilized and the diffusion coefficient of Ca2 is reduced fivefold, due to a high degree of tortuosity; and 2) in the rest of the terminal, the diffusion coefficient of Fura-2 is reduced 100-fold (presumably because of binding to various cytosolic compounds). Moreover, contrary to the statement by Tang et al. that their model fails to accurately describe the accumulation time course of STF, we show that the model modifications that we propose lead to a supralinear growth of STF, in agreement with experiment (Fig. 2, A and D).