Meinrenken Christoph J, Borst J Gerard G, Sakmann Bert
Max Planck Institute for Medical Research, Heidelberg, Germany.
J Physiol. 2003 Mar 15;547(Pt 3):665-89. doi: 10.1113/jphysiol.2002.032714. Epub 2003 Jan 31.
During the last decade, advances in experimental techniques and quantitative modelling have resulted in the development of the calyx of Held as one of the best preparations in which to study synaptic transmission. Here we review some of these advances, including simultaneous recording of pre- and postsynaptic currents, measuring the Ca2+ sensitivity of transmitter release, reconstructing the 3-D anatomy at the electron microscope (EM) level, and modelling the buffered diffusion of Ca2+ in the nerve terminal. An important outcome of these studies is an improved understanding of the Ca2+ signal that controls phasic transmitter release. This article illustrates the spatial and temporal aspects of the three main steps in the presynaptic signalling cascade: Ca2+ influx through voltage-gated calcium channels, buffered Ca2+ diffusion from the channels to releasable vesicles, and activation of the Ca2+ sensor for release. Particular emphasis is placed on how presynaptic Ca2+ buffers affect the Ca2+ signal and thus the amplitude and time course of the release probability. Since many aspects of the signalling cascade were first conceived with reference to the squid giant presynaptic terminal, we include comparisons with the squid model and revisit some of its implications. Whilst the characteristics of buffered Ca2+ diffusion presented here are based on the calyx of Held, we demonstrate the circumstances under which they may be valid for other nerve terminals at mammalian CNS synapses.
在过去十年中，实验技术和定量建模的进展使得海氏壶腹成为研究突触传递的最佳标本之一。在此，我们回顾其中的一些进展，包括同时记录突触前和突触后电流、测量递质释放的Ca2+敏感性、在电子显微镜（EM）水平重建三维解剖结构以及模拟Ca2+在神经末梢中的缓冲扩散。这些研究的一个重要成果是对控制相位性递质释放的Ca2+信号有了更好的理解。本文阐述了突触前信号级联反应中三个主要步骤的空间和时间方面：Ca2+通过电压门控钙通道内流、Ca2+从通道到可释放囊泡的缓冲扩散以及释放的Ca2+传感器的激活。特别强调了突触前Ca2+缓冲剂如何影响Ca2+信号，进而影响释放概率的幅度和时间进程。由于信号级联反应的许多方面最初是参照乌贼巨大突触前末梢构想出来的，我们将其与乌贼模型进行了比较，并重新审视了其中的一些含义。虽然此处介绍的Ca2+缓冲扩散特性基于海氏壶腹，但我们也展示了它们在哪些情况下可能适用于哺乳动物中枢神经系统突触的其他神经末梢。
