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首页> 外文期刊>The European Journal of Neuroscience >AMPA receptor activation induces association of G-beta protein with the alpha subunit of the sodium channel in neurons.
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AMPA receptor activation induces association of G-beta protein with the alpha subunit of the sodium channel in neurons.

机译:AMPA受体激活诱导G-β蛋白与神经元钠通道的α亚基缔合。

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摘要

Glutamatergic transmission is mediated by ionotropic receptors that directly gate cationic channels and metabotropic receptors that are coupled to second messenger generating systems and to ionic channels via heterotrimeric guanine-nucleotide binding- (G) proteins. This distinction cannot be made for the ionotropic receptor subclass activated by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), which has been shown to be physically associated with the alpha-subunit of Gi1 protein and activates this G-protein. Here, we report that, in addition to a Ca2+ influx, AMPA induces the mobilization of Ca2+ from the mitochondrial pool by reversing the mitochondrial Na+/Ca2+ exchanger in mouse neurons in primary culture. Both processes required the activation of tetrodotoxin-sensitive Na+ channels. AMPA receptor activation modified the gating properties of the Na+ channel, independently of the AMPA current, suggesting a G-protein-mediated process. Indeed, co-immunoprecipitation experiments indicated that AMPA receptor activation induced the association of Gbeta with the alpha-subunit of the Na+ channel. These results suggest that, in addition to its ionic channel function, the AMPA receptor is coupled to Na+ channels through G-proteins and that this novel metabotropic function is involved in the control of neuronal excitability.
机译:谷氨酸能传递是通过直接控制阳离子通道和代谢型受体的离子型受体介导的,所述阳离子型通道和代谢型受体通过异三聚体鸟嘌呤-核苷酸结合-(G)蛋白偶联至第二信使产生系统和离子通道。对于由α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)激活的离子型受体亚类无法进行区分,该物质已显示与Gi1蛋白的α亚基物理结合并激活这种G蛋白。在这里,我们报告说,除了Ca2 +大量涌入外,AMPA还通过逆转原代培养小鼠神经元中的线粒体Na + / Ca2 +交换子来诱导线粒体池中Ca2 +的动员。这两个过程都需要激活河豚毒素敏感的Na +通道。 AMPA受体激活独立于AMPA电流而修饰了Na +通道的门控特性,表明G蛋白介导的过程。确实,免疫共沉淀实验表明AMPA受体激活诱导了Gbeta与Na +通道的α-亚基的缔合。这些结果表明,除了其离子通道功能外,AMPA受体还通过G蛋白与Na +通道偶联,并且这种新型的代谢功能与神经元兴奋性的控制有关。

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