Modulation of excitatory synaptic transmission by glycine and zinc in cultures of mouse hippocampal neurons
Modulation of excitatory synaptic transmission by glycine and zinc in cultures of mouse hippocampal neurons
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DOI：
10.1523/jneurosci.08-10-03733.1988
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发表时间：
1988-10
期刊：
影响因子：
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通讯作者：
I. Forsythe;G. Westbrook;M. Mayer
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文献类型：
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作者：
I. Forsythe;G. Westbrook;M. Mayer
培养的海马神经元之间的单突触EPSP是通过激活两类兴奋性氨基酸受体介导的。Kainate或QuisQualate受体产生快速的常规EPSP，而NMDA受体介导缓慢的、电压敏感的EPSP。最近，有两种物质被证明可以调节NMDA受体-通道复合体的活性：甘氨酸增加通道开放的可能性，而锌作为非竞争性拮抗剂。由于这些物质存在于中枢神经系统中，因此可能作为神经调节剂发挥作用，我们使用全细胞膜片记录技术研究了它们在海马区培养的兴奋性突触传递中的作用。缓慢的NMDA受体介导的EPSP明显依赖于在生理盐水中孵育30分钟后逐渐积累在细胞外液中的条件性物质的存在。洗涤条件培养液消除慢的EPSP，用含有1微米甘氨酸的生理盐水灌流使慢的EPSP恢复到对照水平。此外，从星形胶质细胞培养中收集的条件培养液也增强了对NMDA的反应。锌(20-50微米)克服了甘氨酸对兴奋性突触传递的增强作用，并导致慢的EPSP可逆性阻断，为锌对兴奋性突触传递的直接作用提供了第一个证据。我们的结果表明，慢的EPSP的表达可能受到几种内源性物质的调节：可以从星形胶质细胞释放的甘氨酸(或类似甘氨酸的物质)的正调节，以及生理水平锌的负调节。
The monosynaptic EPSP between cultured hippocampal neurons is mediated by activation of 2 classes of excitatory amino acid receptors. Kainate or quisqualate receptors generate a fast conventional EPSP, while NMDA receptors mediate a slow, voltage-sensitive EPSP. Recently, 2 substances have been shown to modulate the activity of the NMDA receptor-channel complex: glycine increases the probability of channel opening, while zinc acts as a noncompetitive antagonist. Since these substances are present in the CNS and thus may function as neuromodulators, we have examined their role in excitatory synaptic transmission in hippocampal cultures using the whole-cell-patch- recording technique. The slow, NMDA-receptor-mediated EPSP was strikingly dependent on the presence of a conditioning substance that gradually accumulated in the extracellular fluid during a 30 min incubation in physiological saline. Washout of the conditioned medium eliminated the slow EPSP, and perfusion with physiological saline containing 1 microM glycine restored the slow EPSP to control levels. Furthermore, conditioned medium collected from astroglial-only cultures also potentiated the response to NMDA. Zinc (20–50 microM) overcame the potentiation of the response by glycine and resulted in a reversible block of the slow EPSP, providing the first evidence for a direct action of zinc on excitatory synaptic transmission. Our results show that the expression of the slow EPSP may be subject to regulation by several endogenous substances: positive modulation by glycine (or a glycine-like substance), which can be released from astroglial cells, and negative modulation by physiological levels of zinc.(ABSTRACT TRUNCATED AT 250 WORDS)