EFFECTS OF NEW NON-N-METHYL-D-ASPARTATE ANTAGONISTS ON SYNAPTIC TRANSMISSION IN THE INVITRO RAT HIPPOCAMPUS
EFFECTS OF NEW NON-N-METHYL-D-ASPARTATE ANTAGONISTS ON SYNAPTIC TRANSMISSION IN THE INVITRO RAT HIPPOCAMPUS
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DOI：
10.1113/jphysiol.1989.sp017690
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发表时间：
1989-07-01
影响因子：
5.5
通讯作者：
JENSEN, MS
中科院分区：
文献类型：
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作者：
ANDREASEN, M;LAMBERT, JDC;JENSEN, MS
1.用细胞内和细胞外记录法研究了新的、有效的非N-甲基-D-天冬氨酸（NMDA）受体拮抗剂6，7-二硝基喹喔啉-2，3-二酮（DNQX）和6-氰基-7-硝基喹喔啉-2，3-二酮（CNQX）的作用。在效力和选择性方面，两种阻断剂的作用相似，并且在大多数实验中使用CNQX。2. CNQX降低了对非NMDA激动剂红藻氨酸盐（KAI）和使君子酸盐（QUIS）的离子电泳应用的响应，IC 50值分别为1.2和4.8 μ M。在不含Mg 2+的溶液中，对NMDA的响应通常不受高达25 μ M的CNQX浓度的影响。3. CNQX的作用仅在洗涤时缓慢且不可逆。响应QUIS和KAI也可逆地减少CNQX的离子电泳应用。4. CNQX以约2 μ M的IC 50阻断CA 1和CA 3神经元中诱发的EPSP，其类似于对KAI应答的IC 50。CNQX不影响被动膜特性，传入齐射和成对脉冲增强。5.在CNQX（>5 μ M）存在下，保留了小的EPSP，其在CA 1神经元中最大。它被低浓度的NMDA受体拮抗剂（. ±.）阻断。2-氨基-5-膦戊酸（APV），并显着增强从浴介质中去除Mg 2+离子，并在电压钳实验中，表现出潜在的依赖性，这是NMDA离子载体的特征。6. CA 1区APV敏感性EPSP的潜伏期与CNQZ敏感性EPSP的潜伏期相同，表明NMDA受体参与单突触兴奋。7. CA 1和CA 3区的反馈和前馈抑制对CNQX敏感。这似乎是抑制的两个组分，两者似乎都是GABA能的，因为它们可以被picortoxin（PTX）阻断，但只有其中一种被CNQX阻断。抗CNQX的IPSP不受APV的影响。8.总之，喹喔啉二酮已被用来证明，非NMDA受体介导的EPSP的大部分。此外，CA 1中EPSP的一个组分由NMDA受体介导，并在静息膜电位和MG 2+存在下表现出来。
1. The effects of new, potent non-N-methyl-D-aspartate (NMDA) receptor antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), have been examined using intra- and extracelluar recordings in the hippocampl slice preparation. In terms of potency and selectivity, the action of the two blockers was similar and CNQX were used in most experiments. 2. CNQX reduced the responses to ionophoretic applications of the non-NMDA agonists kainate (KAI) and quisqualate (QUIS) with IC50 values of 1.2 and 4.8 .mu.M, respectively. In Mg2+-free solutions responses to NMDA were generally not affected by concentration s of CNQX up to 25 .mu.m. 3. The action of CNQX was only slowly and poorly reversible on washing. Responses to QUIS and KAI were also reversibly reduced by ionophoretic application of CNQX. 4. CNQX blocked the evoked EPSP in CA1 and CA3 neurons with an IC50 of around 2 .mu.M, which is similar to the IC50 for responses to KAI. CNQX was without effect on the passive membrane properties, the afferent volley and paired pulse potentiation. 5. In the presence of CNQX (>5 .mu.M) a small EPSP remained which was largest in CA1 neruons. It was blocked by low concentrations of the NMDA receptor antagonist (.+-.)-2-amino-5-posphonovaleric acid (APV) and was markedly enhanced on removing Mg 2+ ions from the bathing medium and, in voltage-clamp experiments, showed a potential dependence which is characteristic of the NMDA ionophore. 6. The latency of the APV-sensitive EPSP in CA1 was the same as the CNQZ-sensitive EPSP, indicating that NMDA receptors participate in monosynaptic excitation. 7. Feedback and feed-forward inhibition in both area CA1 and CA3 were sensitive to CNQX. These seemed to be two components of the inhibition, both of which appear to be GABAergic since they could be blocked by picortoxin (PTX), but only one of which was blocked by CNQX. The CNQX-resistant IPSP was not affected by APV. 8. In conclusion, quinoxlinediones have been used to demonstrate that non-NMDA receptors mediate the majority of the EPSP. Additionally, a component of the EPSP in CA1 is mediated by NMDA receptors and is manifested at resting membrane potentials and in the presence of MG2+.