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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Citrate modulates the regulation by Zn2+ of N-methyl-D-aspartate receptor-mediated channel current and neurotransmitter release.
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Citrate modulates the regulation by Zn2+ of N-methyl-D-aspartate receptor-mediated channel current and neurotransmitter release.

机译：柠檬酸调节N-甲基-D-天冬氨酸受体介导的通道电流和神经递质释放的Zn2 +调节。

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摘要

The effect of the two metal-ion chelators EDTA and citrate on the action of N-methyl-D-aspartate (NMDA) receptors was investigated by use of cultured mouse cerebellar granule neurons and Xenopus oocytes, respectively, to monitor either NMDA-evoked transmitter release or membrane currents. Transmitter release from the glutamatergic neurons was determined by superfusion of the cells after preloading with the glutamate analogue D-[3H]aspartate. The oocytes were injected with mRNA isolated from mouse cerebellum and, after incubation to allow translation to occur, currents mediated by NMDA were recorded electrophysiologically by voltage clamp at a holding potential of -80 mV. It was found that citrate as well as EDTA could attenuate the inhibitory action of Zn2+ on NMDA receptor-mediated transmitter release from the neurons and membrane currents in the oocytes. These effects were specifically related to the NMDA receptor, since the NMDA receptor antagonist MK-801 abolished the action and no effects of Zn2+ and its chelators were observed when kainate was used to selectively activate non-NMDA receptors. Since it was additionally demonstrated that citrate (and EDTA) preferentially chelated Zn2+ rather than Ca2+, the present findings strongly suggest that endogenous citrate released specifically from astrocytes into the extracellular space in the brain may function as a modulator of NMDA receptor activity. This is yet another example of astrocytic influence on neuronal activity.
机译：分别通过使用培养的小鼠小脑颗粒神经元和爪蟾卵母细胞来监测两种NMDA诱发的递质，研究了两种金属离子螯合剂EDTA和柠檬酸对N-甲基-D-天冬氨酸（NMDA）受体的作用释放或膜电流。通过谷氨酸类似物D- [3H]天冬氨酸的预加载后细胞的融合确定了谷氨酸能神经元的递质释放。向卵母细胞注射从小鼠小脑分离的mRNA，在温育以允许翻译发生后，通过电压钳以-80mV的保持电势通过电生理记录由NMDA介导的电流。已经发现柠檬酸盐和EDTA可以减弱Zn 2+对NMDA受体介导的递质从卵母细胞的神经元和膜电流释放的抑制作用。这些作用与NMDA受体特别相关，因为当使用海藻酸盐选择性激活非NMDA受体时，NMDA受体拮抗剂MK-801消除了该作用，并且未观察到Zn2 +及其螯合剂的作用。由于还证明了柠檬酸盐（和EDTA）优先螯合Zn2 +而不是Ca2 +，因此本研究结果强烈表明，从星形胶质细胞释放到大脑细胞外空间的内源性柠檬酸盐可能起着NMDA受体活性的调节剂的作用。这是星形细胞对神经元活动的影响的另一个例子。

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