Residual bound Ca2+ can account for the effects of Ca2+ buffers on synaptic facilitation
Residual bound Ca2+ can account for the effects of Ca2+ buffers on synaptic facilitation
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DOI：
10.1152/jn.00101.2006
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发表时间：
2006-12-01
影响因子：
2.5
通讯作者：
Sherman, Arthur
中科院分区：
文献类型：
--
作者：
Matveev, Victor;Bertram, Richard;Sherman, Arthur
促进是一种短暂的刺激引起的突触反应增加，是一种普遍存在的短期突触可塑性形式，可以在快速时间尺度上调节突触传递。在他们的开创性工作中，Katz， Miledi和rahammoff证明了促进作用对突触前Ca2+内流的依赖性，并提出促进作用是由与囊泡释放触发器结合的残余Ca2+积累引起的。然而，这种结合Ca2+的假设似乎与外源性Ca2+缓冲液降低促进作用的证据相矛盾。这一结论导致了一个广泛持有的观点，即促进必须完全依赖于Ca2+在自由形式的积累。在这里，我们考虑了结合Ca2+机制的更现实的实现，考虑到Ca2+的空间扩散，并表明具有缓慢Ca2+解绑定步骤的模型可以保留对自由残余Ca2+的敏感性。我们证明，该模型与小龙虾抑制剂神经肌肉连接（NMJ）所表现出的促进积累时间过程及其双相衰减一致，并且依赖于比最新的游离残留Ca2+假设变体更少的假设。此外，我们发现结合的Ca2+积累与Kamiya和Zucker的实验结果一致，该实验结果表明，快速Ca2+缓冲液的光解释放在几毫秒内降低了突触反应。我们得出结论，Ca2+结合过程缓慢的解结合时间（几十到几百毫秒）构成了一些突触突触促进的可行机制，并讨论了这种机制的实验证据。
Facilitation is a transient stimulation- induced increase in synaptic response, a ubiquitous form of short- term synaptic plasticity that can regulate synaptic transmission on fast time scales. In their pioneering work, Katz and Miledi and Rahamimoff demonstrated the dependence of facilitation on presynaptic Ca2+ influx and proposed that facilitation results from the accumulation of residual Ca2+ bound to vesicle release triggers. However, this bound Ca2+ hypothesis appears to contradict the evidence that facilitation is reduced by exogenous Ca2+ buffers. This conclusion led to a widely held view that facilitation must depend solely on the accumulation of Ca2+ in free form. Here we consider a more realistic implementation of the bound Ca2+ mechanism, taking into account spatial diffusion of Ca2+, and show that a model with slow Ca2+ unbinding steps can retain sensitivity to free residual Ca2+. We demonstrate that this model agrees with the facilitation accumulation time course and its biphasic decay exhibited by the crayfish inhibitor neuromuscular junction (NMJ) and relies on fewer assumptions than the most recent variants of the free residual Ca2+ hypothesis. Further, we show that the bound Ca2+ accumulation is consistent with Kamiya and Zucker's experimental results, which revealed that photolytic liberation of a fast Ca2+ buffer decreases the synaptic response within milliseconds. We conclude that Ca2+ binding processes with slow unbinding times (tens to hundreds of milliseconds) constitute a viable mechanism of synaptic facilitation at some synapses and discuss the experimental evidence for such a mechanism.