Kim Sang Jeong, Kim Yu Shin, Yuan Joseph P, Petralia Ronald S, Worley Paul F, Linden David J
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA.
Nature. 2003 Nov 20;426(6964):285-91. doi: 10.1038/nature02162. Epub 2003 Nov 12.
Group I metabotropic glutamate receptors (consisting of mGluR1 and mGluR5) are G-protein-coupled neurotransmitter receptors that are found in the perisynaptic region of the postsynaptic membrane. These receptors are not activated by single synaptic volleys but rather require bursts of activity. They are implicated in many forms of neural plasticity including hippocampal long-term potentiation and depression, cerebellar long-term depression, associative learning, and cocaine addiction. When activated, group I mGluRs engage two G-protein-dependent signalling mechanisms: stimulation of phospholipase C and activation of an unidentified, mixed-cation excitatory postsynaptic conductance (EPSC), displaying slow activation, in the plasma membrane. Here we report that the mGluR1-evoked slow EPSC is mediated by the TRPC1 cation channel. TRPC1 is expressed in perisynaptic regions of the cerebellar parallel fibre-Purkinje cell synapse and is physically associated with mGluR1. Manipulations that interfere with TRPC1 block the mGluR1-evoked slow EPSC in Purkinje cells; however, fast transmission mediated by AMPA-type glutamate receptors remains unaffected. Furthermore, co-expression of mGluR1 and TRPC1 in a heterologous system reconstituted a mGluR1-evoked conductance that closely resembles the slow EPSC in Purkinje cells.
I 型代谢型谷氨酸受体（由 mGluR1 和 mGluR5 组成）是 G 蛋白偶联神经递质受体，存在于突触后膜的突触周围区域。这些受体不会被单个突触放电激活，而是需要一连串的活动。它们与多种形式的神经可塑性有关，包括海马体长期增强和抑制、小脑长期抑制、联想学习和可卡因成瘾。激活后，I 型 mGluRs 参与两种 G 蛋白依赖性信号传导机制：刺激磷脂酶 C 和激活一种未确定的、混合阳离子兴奋性突触后电导（EPSC），在质膜中表现出缓慢激活。在这里，我们报告 mGluR1 诱发的缓慢 EPSC 由 TRPC1 阳离子通道介导。TRPC1 在小脑平行纤维 - 浦肯野细胞突触的突触周围区域表达，并与 mGluR1 存在物理关联。干扰 TRPC1 的操作会阻断浦肯野细胞中 mGluR1 诱发的缓慢 EPSC；然而，由 AMPA 型谷氨酸受体介导的快速传递不受影响。此外，mGluR1 和 TRPC1 在异源系统中的共表达重建了一种与浦肯野细胞中缓慢 EPSC 非常相似的 mGluR1 诱发的电导。
