D'Angelo E, Rossi P, Garthwaite J
Department of Physiology, University of Liverpool, UK.
Nature. 1990 Aug 2;346(6283):467-70. doi: 10.1038/346467a0.
Present thinking about the way that the NMDA (N-methyl-D-aspartate) class of glutamate receptor operates at central synapses relies mainly on information obtained from single-channel and whole-cell recordings from cultured neurons stimulated by exogenous NMDA receptor agonists. The mechanisms that operate in the postsynaptic membrane of a normal neuron following release of the natural transmitter are far less clear. An important problem is that most normal neurons receive many excitatory synapses (10(3)-10(5) per cell) and these synapses are located on slender dendritic elements far away from the somatic recording site, making the study of discrete synaptic events difficult. Typically, when populations of synapses are activated, NMDA receptor-mediated synaptic potentials appear as slowly rising, long-lasting waves superimposed on faster, non-NMDA-receptor potentials. Although believed to be critical for NMDA receptor function, this slow time-course would not be predicted from single-channel kinetics and its origin remains puzzling. We have now analysed the events occurring at the level of a single excitatory synapse using a simple, small, neuron--the cerebellar granule cell--which has an unusually simple glutamatergic input. By applying high-resolution whole-cell recording techniques to these cells in situ, we were able to study the nature of elementary NMDA receptor-mediated synaptic currents. Contrary to expectations, the prominent currents are fast but are followed by slow ones. Both types of current are strongly voltage-dependent but differ subtly in this respect. Furthermore, the currents are absent unless glycine is provided.
目前关于N-甲基-D-天冬氨酸（NMDA）类谷氨酸受体在中枢突触发挥作用方式的观点，主要依赖于从培养神经元中外源性NMDA受体激动剂刺激下的单通道和全细胞记录所获得的信息。正常神经元释放天然递质后，在其突触后膜起作用的机制则远不清楚。一个重要问题是，大多数正常神经元会接收许多兴奋性突触（每个细胞10³-10⁵个），且这些突触位于远离体细胞记录位点的细长树突结构上，这使得对离散突触事件的研究变得困难。通常，当一群突触被激活时，NMDA受体介导的突触电位表现为缓慢上升、持续时间长的波，叠加在更快的非NMDA受体电位之上。尽管人们认为这对NMDA受体功能至关重要，但从单通道动力学无法预测这种缓慢的时间进程，其起源仍然令人困惑。我们现在使用一种简单的小型神经元——小脑颗粒细胞，它具有异常简单且谷氨酸能的输入，来分析单个兴奋性突触水平上发生的事件。通过将高分辨率全细胞记录技术应用于这些原位细胞，我们能够研究基本的NMDA受体介导的突触电流的性质。与预期相反，突出的电流是快速出现的，但随后会有缓慢的电流。这两种类型的电流都强烈依赖电压，但在这方面存在细微差异。此外，除非提供甘氨酸，否则不会出现这些电流。
