SYNAPTIC ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS IN THE PARALLEL FIBER-PURKINJE CELL PATHWAY IN RAT CEREBELLAR SLICES
SYNAPTIC ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS IN THE PARALLEL FIBER-PURKINJE CELL PATHWAY IN RAT CEREBELLAR SLICES
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DOI：
10.1016/0306-4522(94)90558-4
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发表时间：
1994-12-01
期刊：
影响因子：
3.3
通讯作者：
GARTHWAITE, J
中科院分区：
文献类型：
--
作者：
BATCHELOR, AM;MADGE, DJ;GARTHWAITE, J
谷氨酸是中枢神经系统中的主要兴奋性神经递质，通过两大类受体发挥作用：离子通道连接受体，包括N-甲基-D-天冬氨酸和alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸受体；代谢性受体，通过G蛋白与细胞内信使级联。已知存在mGluR的七种亚型，但它们在突触生理学中的作用鲜为人知。在小脑浦肯野细胞中，应用mGluR激动剂，反式-1-氨基环戊烷-1，3-二羧酸，或活性对映体，1S，3R-acpd，导致与内向电流(7，26)和细胞内钙离子升高相关的去极化。29)。此外，利用监测群体反应的细胞外(油脂-间隙)技术，我们先前发现，在成年大鼠小脑浦肯野细胞中，对谷氨酸能平行纤维输入的短暂强直刺激产生一种缓慢去极化的突触电位，该电位对离子型谷氨酸受体阻滞剂和作用于GABA受体的拮抗剂具有抵抗力。(2)有人认为这一新的电位是由亲代谢性受体介导的。代谢性受体拮抗剂的出现使我们得以检验这一假说。我们发现α-甲基-4-羧基苯甘氨酸的S对体选择性地拮抗用油隙法记录的慢突触电位。浦肯野细胞的细胞内记录证实了这一结果。据我们所知，这是mGluR介导的EPSP在完整脑组织中的第一个直接证据。
Glutamate, the major excitatory neurotransmitter in the central nervous system, acts through two broad classes of receptors: ion channel-Linked (ionotropic) receptors, which include N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and metabotropic receptors which couple via G-proteins to intracellular messenger cascades. Seven subtypes of mGluR are known to exist(21) but their roles in synaptic physiology are poorly understood. In cerebellar Purkinje cells, application of the mGluR agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid, or the active enantiomer, 1S,3R-ACPD, results in a depolarization associated with an inward current(7,26) and an elevation of intracellular Ca2+ (for review see Ref. 29). Moreover, using an extracellular (grease-gap) technique that monitors population responses, we have previously discovered that, in Purkinje cells of adult rat cerebellum, brief tetanic stimulation of the glutamatergic parallel fibre input gives rise to a slow depolarising synaptic potential that is resistant to ionotropic glutamate receptor blockers and to antagonists acting at GABA receptors.(2) It was suggested that this novel potential is mediated by metabotropic receptors. The advent of antagonists for metabotropic receptors(4) has allowed us to test this hypothesis. We find that the S-enantiomer of alpha-methyl-4-carboxyphenylglycine stereoselectively antagonizes the slow synaptic potential recorded using the grease-gap method. The results were confirmed by intracellular recording from Purkinje cells. To our knowledge this is the first direct evidence of an mGluR-mediated EPSP in intact brain tissue.