Facilitation through buffer saturation: Constraints on endogenous buffering properties
Facilitation through buffer saturation: Constraints on endogenous buffering properties
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DOI：
10.1016/s0006-3495(04)74324-6
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发表时间：
2004-05-01
影响因子：
3.4
通讯作者：
Sherman, A
中科院分区：
文献类型：
--
作者：
Matveev, V;Zucker, RS;Sherman, A
突触促进（SF）是一种普遍存在的短期可塑性形式，在快速时间尺度上调节突触动力学。虽然已知SF依赖于突触前Ca2+的积累，但其确切机制仍在争论中。最近，Klingauf和Neher（1997）提出，在某些中枢突触，SF至少部分是由内源性Ca2+缓冲液的逐渐饱和引起的（Blatow等，2003）。通过计算机模拟，我们研究了缓冲饱和机制（BSM）所能达到的缓冲强度，并探讨了其与内源性缓冲特性的依赖关系。我们发现，高SF值可以通过整个突触前末端高度移动缓冲的整体饱和或完全固定缓冲的局部饱和来获得。在这两种情况下，BSM的一个特征是SF的大小非单调地依赖于缓冲液的浓度。与Blatow等人（2003）的结果一致，我们发现SF随着与Ca2+通道簇的距离增加而增加，并且随着外部Ca2+， [Ca2+]（文本）的增加而增加，对于低水平的[Ca2+]（文本）。我们将建模结果与小龙虾神经肌肉连接处的SF实验特性进行了比较，发现内源性移动缓冲液的饱和度可以解释观察到的SF大小及其超线性积累时间过程。然而，我们表明，在外源性Ca2+缓冲液的存在下，BSM预测SF衰减率会减慢，这与小龙虾神经肌肉连接处的实验观察相反。需要进一步的建模和数据来解决BSM的这方面问题。
Synaptic facilitation (SF) is a ubiquitous form of short-term plasticity, regulating synaptic dynamics on fast timescales. Although SF is known to depend on the presynaptic accumulation of Ca2+, its precise mechanism is still under debate. Recently it has been shown that at certain central synapses SF results at least in part from the progressive saturation of an endogenous Ca2+ buffer (Blatow et al., 2003), as proposed by Klingauf and Neher (1997). Using computer simulations, we study the magnitude of SF that can be achieved by a buffer saturation mechanism (BSM), and explore its dependence on the endogenous buffering properties. We find that a high SF magnitude can be obtained either by a global saturation of a highly mobile buffer in the entire presynaptic terminal, or a local saturation of a completely immobilized buffer. A characteristic feature of BSM in both cases is that SF magnitude depends nonmonotonically on the buffer concentration. In agreement with results of Blatow et al. (2003), we find that SF grows with increasing distance from the Ca2+ channel cluster, and increases with increasing external Ca2+, [Ca2+](text), for small levels of [Ca2+](text). We compare our modeling results with the experimental properties of SF at the crayfish neuromuscular junction, and find that the saturation of an endogenous mobile buffer can explain the observed SF magnitude and its supralinear accumulation time course. However, we show that the BSM predicts slowing of the SF decay rate in the presence of exogenous Ca2+ buffers, contrary to experimental observations at the crayfish neuromuscular junction. Further modeling and data are required to resolve this aspect of the BSM.