Huang Yanhua H, Dykes-Hoberg Margaret, Tanaka Kohichi, Rothstein Jeffrey D, Bergles Dwight E
Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205, USA.
J Neurosci. 2004 Jan 7;24(1):103-11. doi: 10.1523/JNEUROSCI.4473-03.2004.
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.
小脑浦肯野细胞（PCs）表达两种谷氨酸转运体，即EAAC1（EAAT3）和EAAT4；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，在缺乏EAAT4的小鼠中，在攀缘纤维（CF）-PC突触处记录到的谷氨酸转运体电流缺失，但在缺乏EAAC1的小鼠中该电流未发生变化，这表明EAAT4优先参与清除CF突触处的谷氨酸。然而，对野生型和转运体基因敲除小鼠的CF突触电流进行比较后发现，离子型谷氨酸受体对先前归因于转运体的电流的贡献超过40%，这表明PCs清除的CF释放的谷氨酸不到10%。负责非转运体成分的受体占CF兴奋性突触后电流（EPSC）的5%，其时间进程较慢，在CF突触处的占有率低于AMPA受体，并且表现出与海人藻酸受体一致的药理学特性。在GluR5基因敲除小鼠中，该电流显著降低，这表明CF对PCs的兴奋涉及两种不同类型的离子型谷氨酸受体，即AMPA受体和含GluR5的海人藻酸受体。
