Quantitative analysis of calcium-dependent vesicle recruitment and its functional role at the calyx of held synapse
Quantitative analysis of calcium-dependent vesicle recruitment and its functional role at the calyx of held synapse
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DOI：
10.1523/jneurosci.4122-07.2007
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发表时间：
2007-12-26
影响因子：
5.3
通讯作者：
Neher, Erwin
中科院分区：
文献类型：
--
作者：
Hosoi, Nobutake;Sakaba, Takeshi;Neher, Erwin
在突触处募集准备释放的囊泡是决定脑中神经元之间信号传导的动力学性质的重要因素之一。已经表明，强烈的突触活动加速了囊泡募集的速率。突触前末梢中钙离子浓度升高（[Ca 2 +]（i））被认为是造成这种效应的原因。然而，[Ca 2 +]（i）和募集之间的精确关系尚未建立，并且在突触活动期间加速募集的功能后果尚未通过实验量化。为了探讨胞内Ca ~（2+）依赖性的囊泡募集和检查其功能作用过程中的列车动作电位（AP）样刺激，我们监测[Ca ~（2+）]（i）和突触反应同时与配对记录在杯的Held突触。我们发现，一个独特的，快速释放的囊泡池补充的速率与[Ca 2 +]（i）线性增加，没有任何明显的协同性。该增加的斜率因子与1合并液/（μ M.s）相似。用钙调素结合肽特异性阻断Ca 2+依赖性募集表明，在100 Hz AP样列车期间，通过这种Ca 2+依赖性募集机制维持稳态EPSC。使用囊泡动力学的简单模型，我们估计稳态期间的募集速率比静息[Ca 2 +]（i）时的速率加速了10倍。我们还可以证明，在我们的实验条件下，在最初的5-15个AP样刺激过程中，释放概率（易化）增加了大约6倍，而不管EPSC抑郁症。
Recruitment of release-ready vesicles at synapses is one of the important factors, which determine dynamic properties of signaling between neurons in the brain. It has been shown that the rate of vesicle recruitment is accelerated by strong synaptic activity. An elevated concentration of calcium ions in the presynaptic terminal ([Ca2+](i)) has been proposed to be responsible for this effect. However, the precise relationship between [Ca2+](i) and recruitment has not been established yet, and the functional consequences of accelerated recruitment during synaptic activity have not been quantified experimentally. To probe the intracellular Ca2+ dependence of vesicle recruitment and to examine its functional role during trains of action potential (AP)-like stimuli, we monitored [Ca2+](i) and synaptic responses simultaneously with paired recordings at the calyx of Held synapse. We found that a distinct, rapidly releasing vesicle pool is replenished with a rate that increases linearly with [Ca2+](i), without any apparent cooperativity. The slope factor for this increase is similar to 1 pool/(mu M.s). Blocking Ca2+-dependent recruitment specifically with a calmodulin binding peptide revealed that the steady-state EPSCs during 100 Hz AP-like trains were maintained through this Ca2+-dependent recruitment mechanism. Using a simple model of vesicle dynamics, we estimated that the recruitment rate accelerated 10-fold during the steady-state compared with the rate at resting[Ca2+](i). We could also demonstrate an approximate sixfold increase in release probability (facilitation) during the initial 5-15 AP-like stimuli of such trains in our experimental condition, regardless of EPSC depression.