MICROMOLAR CONCENTRATIONS OF ZN-2+ ANTAGONIZE NMDA AND GABA RESPONSES OF HIPPOCAMPAL-NEURONS
MICROMOLAR CONCENTRATIONS OF ZN-2+ ANTAGONIZE NMDA AND GABA RESPONSES OF HIPPOCAMPAL-NEURONS
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DOI：
10.1038/328640a0
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发表时间：
1987-08-13
期刊：
影响因子：
64.8
通讯作者：
MAYER, ML
中科院分区：
文献类型：
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作者：
WESTBROOK, GL;MAYER, ML
NMDA（N-甲基-D-天冬氨酸）受体作为哺乳动物中枢神经系统 (CNS) 突触传递的调节剂，具有短期和长期作用1。二价阳离子对于确定这种行为至关重要，因为 Mg2+ 以电压依赖性方式阻断离子通道2,3，而 Ca2+ 渗透 NMDA 通道4。 Zn2+ 还可以调节神经元兴奋性，因为它在大脑中以高浓度存在，尤其是海马中苔藓纤维的突触小泡5,6，并随着神经元活动而释放7,8。 Zn2+ 的促惊厥 9 和镇静 10 作用均已被报道。我们发现锌是培养海马神经元 NMDA 反应的有效非竞争性拮抗剂。与 Mg2+ 不同，Zn2+ 的作用在 -40 至 +60 mV 之间对电压不敏感，这表明 Zn2+ 和 Mg2+ 在不同的位点起作用。此外，我们还发现 Zn2+ 可以拮抗抑制性递质 GABA（γ-氨基丁酸）的反应。我们的结果为 NMDA 受体通道上存在额外的金属结合位点提供了证据，并表明 Zn2+ 可能调节海马的兴奋性和抑制性突触传递。
NMDA (N-methyl-D-aspartate) receptors serve as modulators of synaptic transmission in the mammalian central nervous system (CNS) with both short-term and long-lasting effects1. Divalent cations are pivotal in determining this behaviour in that Mg2+blocks the ion channel in a voltage-dependent manner2,3, and Ca2+permeates NMDA channels4. Zn2+could also modulate neuronal excitability because it is present at high concentrations in brain, especially the synaptic vesicles of mossy fibres in the hippocampus5,6and is released with neuronal activity7,8. Both proconvulsant9and depressant10actions of Zn2+have been reported. We have found that zinc is a potent non-competitive antagonist of NMDA responses on cultured hippocampal neurons. Unlike Mg2+, the effect of Zn2+is not voltage-sensitive between −40 and +60 mV, suggesting that Zn2+and Mg2+act at distinct sites. In addition, we have found that Zn2+antagonizes responses to the inhibitory transmitter GABA (γ-aminobutyric acid). Our results provide evidence for an additional metal-binding site on the NMDA receptor channel, and suggest that Zn2+may regulate both excitatory and inhibitory synaptic transmission in the hippocampus.