Otsu Yo, Shahrezaei Vahid, Li Bo, Raymond Lynn A, Delaney Kerry R, Murphy Timothy H
Kinsmen Laboratory and Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
J Neurosci. 2004 Jan 14;24(2):420-33. doi: 10.1523/JNEUROSCI.4452-03.2004.
Developing hippocampal neurons in microisland culture undergo rapid and extensive transmitter release-dependent depression of evoked (phasic) excitatory synaptic activity in response to 1 sec trains of 20 Hz stimulation. Although evoked phasic release was attenuated by repeated stimuli, asynchronous (miniature like) release continued at a high rate equivalent to approximately 2.8 readily releasable pools (RRPs) of quanta/sec. Asynchronous release reflected the recovery and immediate release of quanta because it was resistant to sucrose-induced depletion of the RRP. Asynchronous and phasic release appeared to compete for a common limited supply of release-ready quanta because agents that block asynchronous release, such as EGTA-AM, led to enhanced steady-state phasic release, whereas prolongation of the asynchronous release time course by LiCl delayed recovery of phasic release from depression. Modeling suggested that the resistance of asynchronous release to depression was associated with its ability to out-compete phasic release for recovered quanta attributable to its relatively low release rate (up to 0.04/msec per vesicle) stimulated by bulk intracellular Ca2+ concentration ([Ca2+]i) that could function over prolonged intervals between successive stimuli. Although phasic release was associated with a considerably higher peak rate of release (0.4/msec per vesicle), the [Ca2+]i microdomains that trigger it are brief (1 msec), and with asynchronous release present, relatively few quanta can accumulate within the RRP to be available for phasic release. We conclude that despite depression of phasic release during train stimulation, transmission can be maintained at a near-maximal rate by switching to an asynchronous mode that takes advantage of a bulk presynaptic [Ca2+]i.
在微岛培养中发育的海马神经元，在受到20 Hz刺激的1秒串刺激时，会经历快速且广泛的、依赖递质释放的诱发（相位性）兴奋性突触活动抑制。尽管重复刺激会使诱发的相位性释放减弱，但异步（类微小）释放仍以相当于约2.8个易释放池（RRP）量子/秒的高速持续进行。异步释放反映了量子的恢复和即时释放，因为它对蔗糖诱导的RRP耗竭具有抗性。异步释放和相位性释放似乎在争夺共同的有限的释放就绪量子供应，因为诸如EGTA - AM等阻断异步释放的试剂会导致稳态相位性释放增强，而LiCl延长异步释放时间进程则会延迟相位性释放从抑制中恢复。模型表明，异步释放对抑制的抗性与其在恢复的量子方面比相位性释放更具竞争力的能力有关，这归因于其相对较低的释放速率（每个囊泡高达0.04/毫秒），该速率由可在连续刺激之间的长时间间隔起作用的胞内Ca2 +浓度（[Ca2 +]i）刺激。尽管相位性释放与相当高的峰值释放速率（每个囊泡0.4/毫秒）相关，但触发它的[Ca2 +]i微区很短暂（1毫秒），并且由于存在异步释放，相对较少的量子能够在RRP内积累以供相位性释放。我们得出结论，尽管在串刺激期间相位性释放受到抑制，但通过切换到利用大量突触前[Ca2 +]i的异步模式，传递仍可维持在接近最大速率。
