Single-domain/bound calcium hypothesis of transmitter release and facilitation
Single-domain/bound calcium hypothesis of transmitter release and facilitation
复制标题
DOI：
10.1152/jn.1996.75.5.1919
复制
发表时间：
1996-05-01
影响因子：
2.5
通讯作者：
Stanley, EF
中科院分区：
文献类型：
--
作者：
Bertram, R;Sherman, A;Stanley, EF
1.我们描述了一个模型的发射机的释放，这是基于发现，释放可以门控在开放的个人钙通道，这表明释放网站可以激活的钙结构域下的一个单一的通道。在该模型中，每个释放位点包含四个独立的Ca 2+结合位点或门，其解结合动力学从慢到快分级，亲和力从高到低。所有四个门必须绑定释放发生。因此，突触动力学是由Ca 2+结合和从释放位点释放的动力学决定的，而不是由Ca 2+扩散决定的.快速易化发生在动作电位侵入一个末端，一个或多个离子保持与释放位点结合。残留的游离Ca 2+对于该机制的易化不是必需的，但如果存在的话，它将通过与脉冲之间的高亲和力门结合来增强易化。该模型可以解释释放的关键特征。这些包括四次幂的协同性方面的外部Ca 2 +;释放时间过程，这是几乎独立的量子含量的增加;外部Ca 2+和促进的程度之间的反比关系;和一个阶梯状的增加，促进与增加刺激频率，与每一步对应的一个单一的下降Ca 2+的协同性。促进单通道的分泌被证明是强大的，即使通道开放是随机的。自发释放的发射机，假设是由于自发的Ca 2+通道开放的一部分，被证明是在一系列的脉冲期间和之后升高。模型的扩展，包括多个Ca 2+通道每个释放网站表明，重叠的Ca 2+域的一个作用可能是强调去极化诱发的释放相对于自发释放。
1. We describe a model of transmitter release that is based on the finding that release can be gated during the opening of individual Ca2+ channels, suggesting that the release site can be activated by the Ca2+ domain under a single channel. In this model each release site contains four independent Ca2+ binding sites or gates with unbinding kinetics graded from slow to fast and affinities ranging from high to low. All four gates must be bound for release to occur. Thus synaptic dynamics are governed by the kinetics of Ca2+ binding and unbinding from release sites, not Ca2+ diffusion.2. Fast facilitation occurs when an action potential invades a terminal with one or more ions remaining bound to the release sites. Residual free Ca2+ is not necessary for facilitation with this mechanism, but if present it would enhance facilitation by binding to high-affinity gates between pulses.3. This model can account for key features of release. These include fourth-power cooperativity with regard to external Ca2+; a release time course that is virtually independent of an increase in quantal content; an inverse relation between external Ca2+ and the degree of facilitation; and a steplike increase in facilitation with increasing stimulus frequency, with each step corresponding to a unitary decline in the Ca2+ cooperativity.4. Facilitation of single-channel-based secretion is shown to be robust even if channel opening is stochastic. Spontaneous release of transmitter, assumed to be due in part to spontaneous Ca2+ channel openings, is shown to be elevated during and after a train of impulses.5. An extension of the model to include multiple Ca2+ channels per release site demonstrates that one role of overlapping Ca2+ domains may be to accentuate depolarization-evoked release relative to spontaneous release.