Baseline glutamate levels affect group I and II mGluRs in layer V pyramidal neurons of rat sensorimotor cortex
Baseline glutamate levels affect group I and II mGluRs in layer V pyramidal neurons of rat sensorimotor cortex
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DOI：
10.1152/jn.00644.2002
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发表时间：
2003-03-01
影响因子：
2.5
通讯作者：
Prince, DA
中科院分区：
文献类型：
--
作者：
Bandrowski, AE;Huguenard, JR;Prince, DA
谷氨酸在完整脑和脑切片的细胞外空间中以低浓度可检测到的可能的功能作用尚未被探索。为了确定这种内源性谷氨酸是否作用于代谢型谷氨酸受体（mGluRs），我们获得了大鼠感觉运动皮层切片的第V层锥体神经元的全细胞记录。用（+）-α-氨基-4-羧基-α-甲基-苯乙酸（MCPG，一种通用的mGluR拮抗剂）阻断mGluR可增加自发兴奋性突触后电流（sEPSC）的平均振幅，该效应可归因于大振幅sEPSC发生率的选择性增加。2S-2-氨基-2-（1 S，2S-2-羧基环丙基-1-基）-3-甲基-IH-吡唑（黄原酸-9-基）丙酸（LY 341495，II组拮抗剂）增加，但R（-）-1-氨基-2，3-二氢-1H-茚-1，5-二羧酸（AIDA）和（RS）-己基-HIBO（I组拮抗剂）降低sEPSC振幅，（R，S）-α-环丙基-4-膦酰基苯基甘氨酸由MCPG、AIDA和LY 341495引起的sEPSC的变化在河豚毒素中不存在，这表明它是动作电位依赖性的。GABA受体拮抗剂中sEPSC的增加持续存在，表明这不是由于对抑制性中间神经元的影响。AIDA和（S）-3，5-二羟基苯甘氨酸（DHPG）分别引起保持电流的正移和负移。LY 341495和（2S，2 'R，3' R）-2-（2 '，3'-dicarboxycyclopropyl）glycine（DCG-IV，一种II类激动剂）分别引起保持电流的负移和正移。AIDA和LY 341495在TTX上诱发的电流持续存在。最后，在电流钳实验中，LY 341495使细胞去极化约2 mV，并增加给定去极化电流脉冲的动作电位数目。因此，环境水平的谷氨酸张力激活mGluRs和调节皮质兴奋性。
Possible functional roles for glutamate that is detectable at low concentrations in the extracellular space of intact brain and brain slices have not been explored. To determine whether this endogenous glutamate acts on metabotropic glutamate receptors (mGluRs), we obtained whole cell recordings from layer V pyramidal neurons of rat sensorimotor cortical slices. Blockade of mGluRs with (+)-alpha-amino-4-carboxy-alpha-methyl-benzeacetic acid (MCPG, a general mGluR antagonist) increased the mean amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), an effect attributable to a selective increase in the occurrence of large amplitude sEPSCs. 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid (LY341495, a group II antagonist) increased, but R(-)-1-amino-2,3-dihydro-1H-indene-1,5-dicarboxylic acid (AIDA) and (RS)-hexyl-HIBO (group I antagonists) decreased sEPSC amplitude, and (R,S)-alpha-cyclopropyl-4-phosphonophenylglycine (CPPG, a group III antagonist) did not change it. The change in sEPSCs elicited by MCPG, AIDA, and LY341495 was absent in tetrodotoxin, suggesting that it was action potential-dependent. The increase in sEPSCs persisted in GABA receptor antagonists, indicating that it was not due to effects on inhibitory interneurons. AIDA and (S)-3,5-dihydroxyphenylglycine (DHPG, a group I agonist) elicited positive and negative shifts in holding current, respectively. LY341495 and (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV, a group II agonist) elicited negative and positive shifts in holding current, respectively. The AIDA and LY341495 elicited currents persisted in TTX. Finally, in current clamp, LY341495 depolarized cells by similar to2 mV and increased the number of action potentials to a given depolarizing current pulse. Thus ambient levels of glutamate tonically activate mGluRs and regulate cortical excitability.