NMDA RECEPTOR CHANNELS - SUBUNIT-SPECIFIC POTENTIATION BY REDUCING AGENTS
NMDA RECEPTOR CHANNELS - SUBUNIT-SPECIFIC POTENTIATION BY REDUCING AGENTS
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DOI：
10.1016/0896-6273(94)90311-5
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发表时间：
1994-05-01
期刊：
影响因子：
16.2
通讯作者：
SEEBURG, PH
中科院分区：
文献类型：
--
作者：
KOHR, G;ECKARDT, S;SEEBURG, PH
巯基氧化还原剂影响NMDA受体活性。我们研究了四个重组NMDA受体中的一个假定的氧化还原位点。在表达NR1NR2A型通道的293细胞中，二硫苏糖醇可迅速增强L谷氨酸激活的全细胞电流，并缩短脱敏和失活的时间进程。部分电流增强(可逆成分)和所有动力学变化在冲刷时被逆转。残留的增强作用(持久成分)被氧化剂消除。NR2A的N端370个残基介导嵌合NR2亚基中的可逆成分。在表达NR1-NR2B、-NR2C和-NR2D通道的细胞中，DTT只引起缓慢发展的持续增强，并延长了失活时间。在这些中，但不是在NR1-NR2A中，DTT效应通过烷基化而变得对再氧化不敏感。还原型谷胱甘肽仅在NR1-NR2a受体上模拟DTT效应。因此，分子上不同的NMDA受体对巯基氧化还原试剂的反应有很大的不同。
Sulfhydryl redox agents affect NMDA receptor activity. We investigated a putative redox site in four recombinant NMDA receptors. In 293 cells expressing NR1-NR2A channels dithiothreitol (DTT) rapidly potentiated L-glutamate-activated whole-cell currents and decreased the time course of desensitization and deactivation. Part of the current potentiation (reversible component) and all kinetic changes reversed upon washout. The remaining potentiation (persistent component) was abolished by an oxidizing agent. The N-terminal 370 residues of NR2A mediate the reversible component in chimeric NR2 subunits. In cells expressing the NR1-NR2B, -NR2C, and -NR2D channels DTT elicited only a slowly developing, persistent potentiation and increased the deactivation time course. In these, but not in NR1-NR2A, the DTT effect was rendered insensitive to reoxidation by alkylation. Reduced glutathione mimicked the DTT effects only in the NR1-NR2A receptor. Hence, molecularly distinct NMDA receptors differ profoundly in their responses to sulfhydryl redox agents.