Vignes M
Laboratoire Plasticité Cérébrale, UMR 5102 CNRS, Université Montpellier II, Place Eugène Bataillon, F-34095 Montpellier Cedex 05, France.
Neuropharmacology. 2001 May;40(6):737-48. doi: 10.1016/s0028-3908(00)00213-6.
The regulation of gamma-aminobutyric acid (GABA)-mediated spontaneous inhibitory synaptic transmission by endogenously released glutamate was studied in cultured rat hippocampal neurons. After 7 days in vitro (DIV), both spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) could be detected. After 15 DIV, most postsynaptic spontaneous currents occurred as sEPSC/sIPSC sequences when recorded at a holding voltage of -30 mV. In the presence of the glutamate alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subtype antagonist LY303070, both the frequency and amplitude of sIPSC were strongly and reversibly reduced. The N-methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP5), had no effect on sIPSC while cyclothiazide strongly increased sIPSC frequency. Under blockade of AMPA receptors, the kainate- and GluR5-selective kainate receptor agonists, (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid) (ATPA) and (S)-5-iodowillardiine (5IWill), induced a large enhancement of the frequency of small-amplitude sIPSC which was blocked by the non-NMDA receptor antagonist, 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX). All of these effects were sensitive to tetrodotoxin (TTX). In the presence of LY303070 and TTX, kainate could induce a small inward current while GluR5 agonists had no effect. In the presence of NMDA and AMPA receptor antagonists, the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (t-PDC) could restore sIPSC. When NBQX was used as an AMPA antagonist, the stimulatory effect of t-PDC was blocked while the group I metabotropic glutamate agonist, 3,5-dihydroxyphenylglycine (DHPG), induced a strong enhancement of sIPSC. Therefore, both AMPA and kainate receptors can regulate inhibitory synaptic transmission in cultured hippocampal neurons, the former by tonic activation, the latter when the glutamate concentration is increased by impairing glutonate uptake.
在培养的大鼠海马神经元中研究了内源性释放的谷氨酸对γ-氨基丁酸（GABA）介导的自发性抑制性突触传递的调节作用。体外培养7天（DIV）后，可检测到自发性兴奋性突触后电流（sEPSCs）和自发性抑制性突触后电流（sIPSCs）。培养15天后，当在-30 mV的钳制电压下记录时，大多数突触后自发电流以sEPSC/sIPSC序列的形式出现。在存在谷氨酸α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体亚型拮抗剂LY303070的情况下，sIPSC的频率和幅度均强烈且可逆地降低。N-甲基-D-天冬氨酸（NMDA）受体拮抗剂2-氨基-5-膦酰基戊酸（AP5）对sIPSC无影响，而环噻嗪可强烈增加sIPSC频率。在AMPA受体被阻断的情况下，海人酸和GluR5选择性海人酸受体激动剂（RS）-2-氨基-3-（3-羟基-5-叔丁基异恶唑-4-基）丙酸（ATPA）和（S）-5-碘威拉地因（5IWill）可诱导小幅度sIPSC频率大幅增加，这被非NMDA受体拮抗剂2,3-二氢-6-硝基-7-氨磺酰基苯并[f]喹喔啉（NBQX）阻断。所有这些效应均对河豚毒素（TTX）敏感。在存在LY303070和TTX的情况下，海人酸可诱导小的内向电流，而GluR5激动剂则无作用。在存在NMDA和AMPA受体拮抗剂的情况下，谷氨酸摄取抑制剂L-反式-吡咯烷-2,4-二羧酸（t-PDC）可恢复sIPSC。当使用NBQX作为AMPA拮抗剂时，t-PDC的刺激作用被阻断，而I组代谢型谷氨酸受体激动剂3,5-二羟基苯甘氨酸（DHPG）可诱导sIPSC强烈增强。因此，AMPA和海人酸受体均可调节培养的海马神经元中的抑制性突触传递，前者通过持续性激活，后者在谷氨酸浓度因谷氨酸摄取受损而增加时发挥作用。
