Excitatory amino acid antagonists inhibit synaptic responses in the guinea pig hypothalamic paraventricular nucleus.
Excitatory amino acid antagonists inhibit synaptic responses in the guinea pig hypothalamic paraventricular nucleus.
复制标题
兴奋性氨基酸拮抗剂抑制豚鼠下丘脑室旁核的突触反应。
DOI：
10.1152/jn.1991.65.4.946
复制
发表时间：
1991
影响因子：
2.5
通讯作者：
Dudek,FE
中科院分区：
文献类型：
--
作者：
Wuarin,JP;Dudek,FE
1.用离体脑片法研究了特异性兴奋性氨基酸（EAA）拮抗剂对豚鼠下丘脑室旁核（PVN）诱发兴奋性突触反应的影响。室旁神经元进行细胞内记录，并通过穹窿周围电刺激诱导兴奋性突触后电位（EPSP）和电流（EPSC）。为了减少潜在的γ-氨基丁酸A（GABAA）抑制成分对突触反应的影响，所有实验都在50 μ M印防己毒素的存在下进行。2.在20个测试细胞中，13个具有类似于大细胞神经肽能细胞（MNCs）的电生理特性，7个显示低阈值Ca 2+峰（LTS）。在有或没有LTS电位的细胞的突触反应的拮抗剂的效果没有发现差异。3.广谱EAA拮抗剂犬尿烯酸以剂量依赖性方式降低EPSP和EPSC的振幅：100 μ M的平均降低5%，300 μ M的平均降低43%，1 mM的平均降低70%。使君子酸/红藻氨酸受体选择性拮抗剂6-氰基-2，3-二羟基-7-硝基喹喔啉（CNQX）诱导了剂量依赖性的EPSP和EPSC减少：1 μ M没有检测到影响，3和10 μ M分别导致30%和70%的减少，30 μ M几乎完全阻断了反应。这种效应并不伴随着静息膜电位或输入电阻的变化，并且是缓慢可逆的。5. N-甲基-D-天冬氨酸（NMDA）受体选择性拮抗剂DL-2-氨基-5-膦酰基戊酸（AP 5），在30和300 μ M的应用，略有减少衰减阶段的EPSP的振幅，但没有显着影响的峰值振幅。在一些细胞中，EPSC的衰减相的电流-电压关系揭示了-70 mV和-40 mV之间的负斜率电导区域。6.这些结果表明：1）谷氨酸或相关的EAA负责PVN中大细胞和小细胞神经元的快速兴奋性输入，可能也负责PVN周围的细胞，2）使君子酸/红藻氨酸受体类型负责突触电流的上升相和峰值幅度，3）NMDA受体有助于突触反应的后期部分。
1. The effects of specific excitatory amino acid (EAA) antagonists on evoked excitatory synaptic responses were studied in the hypothalamic paraventricular nucleus (PVN) of the guinea pig, by the use of the in vitro slice preparation. Intracellular recordings were obtained from paraventricular neurons, and excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) were induced by perifornical electrical stimulation. To reduce the influence of a potential gamma-aminobutyric acidA (GABAA) inhibitory component on the synaptic responses, all experiments were performed in the presence of 50 microM picrotoxin. 2. Of 20 cells tested, 13 had electrophysiological characteristics similar to magnocellular neuropeptidergic cells (MNCs) and 7 displayed low-threshold Ca2+ spikes (LTSs). No difference was detected in the effect of the antagonists on the synaptic responses of cells with or without LTS potentials. 3. The broad-spectrum EAA antagonist kynurenic acid decreased the amplitude of the EPSPs and EPSCs in a dose-dependent manner: the mean decrease was 5% for 100 microM, 43% for 300 microM, and 70% for 1 mM. 4. The quisqualate/kainate-receptor-selective antagonist 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) induced a dose-dependent decrease of the EPSPs and EPSCs: 1 microM had no detectable effect, 3 and 10 microM caused 30 and 70% decreases, respectively, and 30 microM blocked the response almost completely. This effect was not accompanied by a change in resting membrane potential or input resistance and was slowly reversible. 5. The N-methyl-D-aspartate (NMDA)-receptor-selective antagonist DL-2-amino-5-phosphonopentanoic acid (AP5), applied at 30 and 300 microM, reduced slightly the amplitude of the decay phase of the EPSP but did not significantly affect the peak amplitude. In some cells, the current-voltage relationship of the decay phase of the EPSC revealed a region of negative slope conductance between -70 and -40 mV. 6. These results suggest that 1) glutamate or a related EAA is responsible for the fast excitatory input to magnocellular and parvocellular neurons in the PVN and probably also for cells around PVN, 2) a quisqualate/kainate receptor type is responsible for the rising phase and peak amplitude of the synaptic current, and 3) an NMDA receptor contributes to the late part of the synaptic response.