Properties of synchronous and asynchronous release during pulse train depression in cultured hippocampal neurons
Properties of synchronous and asynchronous release during pulse train depression in cultured hippocampal neurons
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DOI：
10.1152/jn.2001.85.6.2324
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发表时间：
2001-06-01
影响因子：
2.5
通讯作者：
Goda, Y
中科院分区：
文献类型：
--
作者：
Hagler, DJ;Goda, Y
神经递质释放表现出至少两种不同的动力学成分，以响应单一的动作电位。大部分释放与动作电位触发的Ca2+内流同步发生；然而，延迟释放-也称为异步释放-在Ca2+瞬态峰值后持续数十毫秒。在动作电位的反应中，同步释放最终下降，而异步释放通常逐渐增加，这种效应主要归因于重复刺激期间细胞内Ca2+的积累。在中枢突触上，同步和异步释放之间的确切关系尚不清楚。为了更好地了解调节神经递质释放的机制，我们系统地表征了在培养中形成的兴奋性自适应海马突触重复刺激时释放的主要成分。操作增加Ca2+内流触发的动作电位-细胞外Ca2+升高或四乙基铵（TEA）浴应用-加速了同步释放（兴奋性突触后电流振幅峰值）的逐步减少，并同时增加了异步释放。当细胞外应用EGTA-AM缓冲细胞内Ca2+时，同步释放的初始抑制等于或大于对照；然而，它很快就达到了一个平台，没有进一步的下降。相比之下，异步释放在EGTA-AM中基本上被废除了。每个脉冲后的总电荷转移（包括同步和异步释放）达到了与对照组和EGTA-AM相似的稳态水平。因此，控制条件下减少的同步释放的一部分与更高级别的异步释放相匹配。我们还研究了在重复刺激期间同步和异步释放的相对变化，在高度支持通过用Sr2+取代细胞外Ca2+的异步释放的条件下。最初，异步发布在Sr2+中要大两倍。到火车结束时，差异接近50%；因此，与Ca2+相比，Sr2+在平台期的每脉冲总释放量略大。因此，我们得出结论，虽然异步释放（类似于同步释放）受到囊泡可用性的限制，但它可能能够访问一个稍大的可释放池子集。我们的结果与重复刺激时，异步释放的升高消耗了立即可用释放的囊泡，导致同步释放的降低的观点一致。这意味着两种形式的释放共享一个小的立即释放囊泡池，在重复刺激中不断消耗和重新填充。
Neurotransmitter release displays at least two kinetically distinct components in response to a single action potential. The majority of release occurs synchronously with action-potential-triggered Ca2+ influx; however, delayed release-also called asynchronous release-persists for tens of milliseconds following the peak Ca2+ transient. In response to trains of action potentials, synchronous release eventually declines, whereas asynchronous release often progressively increases, an effect that is primarily attributed to the buildup of intracellular Ca2+ during repetitive stimulation. The precise relationship between synchronous and asynchronous release remains unclear at central synapses. To gain better insight into the mechanisms that regulate neurotransmitter release, we systematically characterized the mio components of release during repetitive stimulation at excitatory autaptic hippocampal synapses formed in culture. Manipulations that increase the Ca2+ influx triggered by an action potential-elevation of extracellular Ca2+ or bath application of tetraethylammonium (TEA)-accelerated the progressive decrease in synchronous release (peak excitatory postsynaptic current amplitude) and concomitantly increased asynchronous release. When intracellular Ca2+ was buffered by extracellular application of EGTA-AM, initial depression of synchronous release was equal to or greater than control; however, it quickly reached a plateau without further depression. In contrast, asynchronous release was largely abolished in EGTA-AM. The total charge transfer following each pulse-accounting for both synchronous and asynchronous release-reached a steady-state level that was similar between control and EGTA-AM. A portion of the decreased synchronous release in control conditions therefore was matched by a higher level of asynchronous release. We also examined the relative changes in synchronous and asynchronous release during repetitive stimulation under conditions that highly favor asynchronous release by substituting extracellular Ca2+ with Sr2+. Initially, asynchronous release was twofold greater in Sr2+. By the end of the train, the difference was similar to 50%; consequently, the total release per pulse during the plateau phase was slightly larger in Sr2+ compared with Ca2+. We thus conclude that while asynchronous release-like synchronous release-is limited by vesicle availability, it may be able to access a slightly larger subset of the readily releasable pool. Our results are consistent with the view that during repetitive stimulation, the elevation of asynchronous release depletes the vesicles immediately available for release, resulting in depression of synchronous release. This implies that both forms of release share a small pool of immediately releasable vesicles, which is being constantly depleted and refilled during repetitive stimulation.