Climbing fiber activation of EAAT4 transporters and kainate receptors in cerebellar Purkinje cells
Climbing fiber activation of EAAT4 transporters and kainate receptors in cerebellar Purkinje cells
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DOI：
10.1523/jneurosci.4473-03.2004
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发表时间：
2004-01-07
影响因子：
5.3
通讯作者：
Bergles, DE
中科院分区：
文献类型：
--
作者：
Huang, YHH;Dykes-Hoberg, M;Bergles, DE
小脑浦肯野细胞（PC）表达两种谷氨酸转运蛋白，EAAC 1（EAAT 3）和EAAT 4;然而，它们对突触处谷氨酸摄取的相对贡献尚不清楚。我们发现，记录在攀爬纤维（CF）-PC突触的谷氨酸转运体电流在缺乏EAAT 4的小鼠中不存在，但在缺乏EAAC 1的小鼠中不变，表明EAAT 4优先参与清除CF突触中的谷氨酸。然而，野生型和转运蛋白敲除小鼠之间的CF突触电流的比较显示，离子型谷氨酸受体负责先前归因于转运蛋白的电流的> 40%，表明PC去除CF释放的谷氨酸的< 10%。负责非转运体成分的受体占CF EPSC的5%，具有较慢的时间过程和较低的占用率比AMPA受体在CF突触，并表现出与红藻氨酸受体一致的药理学特性。在GluR 5基因敲除小鼠中，该电流显著降低，表明PC的CF激发涉及两种不同类型的离子型谷氨酸受体，AMPA受体和含GluR 5的红藻氨酸受体。
Cerebellar Purkinje cells (PCs) express two glutamate transporters, EAAC1 (EAAT3) and EAAT4; however, their relative contribution to the uptake of glutamate at synapses is not known. We found that glutamate transporter currents recorded at climbing fiber (CF)-PC synapses are absent in mice lacking EAAT4 but unchanged in mice lacking EAAC1, indicating that EAAT4 is preferentially involved in clearing glutamate from CF synapses. However, comparison of CF synaptic currents between wild-type and transporter knock-out mice revealed that ionotropic glutamate receptors are responsible for > 40% of the current previously attributed to transporters, indicating that PCs remove < 10% of the glutamate released by the CF. The receptors responsible for the nontransporter component accounted for 5% of the CF EPSC, had a slower time course and lower occupancy than AMPA receptors at CF synapses, and exhibited pharmacological properties consistent with kainate receptors. In GluR5 knock-out mice, this current was dramatically reduced, indicating that CF excitation of PCs involves two distinct classes of ionotropic glutamate receptors, AMPA receptors and GluR5-containing kainate receptors.