The NMDA receptor antagonist 2-amino-5-phosphonovalerate blocks stimulus train-induced epileptogenesis but not epileptiform bursting in the rat hippocampal slice.
The NMDA receptor antagonist 2-amino-5-phosphonovalerate blocks stimulus train-induced epileptogenesis but not epileptiform bursting in the rat hippocampal slice.
复制标题
NMDA 受体拮抗剂 2-氨基-5-磷酸戊酸可阻断刺激序列诱导的癫痫发生，但不会阻断大鼠海马切片中的癫痫样爆发。
DOI：
10.1152/jn.1987.57.1.1
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发表时间：
1987
影响因子：
2.5
通讯作者：
Wilson,WA
中科院分区：
文献类型：
--
作者：
Anderson,WW;Swartzwelder,HS;Wilson,WA
在大鼠海马CA 3区观察了N-甲基-D-天冬氨酸（NMDA）受体在刺激串诱发爆发（STIB）中的作用。从CA 3锥体细胞层进行细胞外记录。通过向CA 3辐射层递送一系列电刺激或通过浴用NMDA诱导爆发。再用特异性NMDA受体拮抗剂DL-2-氨基-5-膦酰基戊酸（APV）阻断STIB和NMDA激活的爆发。NMDA激活的剂量-反应关系表明，浴应用1和5 μ M的NMDA对成对刺激脉冲（触发反应）的反应几乎没有影响，也没有诱导自发爆发。10微摩尔的NMDA诱导强烈的触发和自发爆裂的应用程序中的NMDA在72%的切片。50 ~ 100 μ mol NMDA可使兴奋性突触后电位（EPSP）和顺向峰电位消失，逆向峰电位减少或消失。在10 μ M NMDA后的正常介质冲洗中，在10 μ M NMDA中产生触发和自发爆发的那些切片经历了兴奋性降低的早期阶段，其中自发爆发仅发生在6%的NMDA爆发的切片中。后来在清洗自发爆发开始发生在一半的片，在NMDA的爆发，和兴奋性的触发爆发略有增加。测试NMDA受体拮抗剂APV阻断NMDA激活的爆发的能力。单独使用100或200 μ M APV的浴槽应用对正常触发反应几乎没有影响。当10 μ M NMDA加入到APV溶液中时，触发反应几乎没有变化或没有变化，并且没有自发爆发发生。然而，当100或500 APV加入到NMDA溶液后，NMDA爆发激活已经发生，触发爆发减少，但不阻断，虽然自发爆发被阻断。在NMDA洗脱后继续爆发的那些切片中，100或500 μ M APV的浴应用减少，但不阻断，触发爆发。在所有切片中继续自发破裂。然后测试APV阻断由一连串电刺激诱导的爆发的能力。（400字处截断摘要）
The role of N-methyl-D-aspartate (NMDA) receptors in producing stimulus train-induced bursting (STIB) was examined in area CA3 of the rat hippocampus. Extracellular recordings were made from the CA3 pyramidal cell layer. Bursting was induced by trains of electrical stimuli delivered to the stratum radiatum of CA3, or by bath application of NMDA. The specific NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) was then bath applied to test its ability to block STIB and NMDA activated bursting. A dose-response relation for NMDA activation indicated that bath application of 1 and 5 microM NMDA had little or no effect on the response to a paired stimulus pulse (triggered response) and did not induce spontaneous bursting. Ten micromolar NMDA induced strong triggered and spontaneous bursting during the application of NMDA in 72% of the slices. Fifty to one hundred micromolar NMDA caused the abolition of the excitatory postsynaptic potential (EPSP) and orthodromic population spike and the decrease or abolition of the antidromic population spike. In the normal medium wash following 10 microM NMDA, those slices that produced triggered and spontaneous bursting in 10 microM NMDA underwent an early phase of decreased excitability in which spontaneous bursting occurred in only 6% of the slices that were bursting in NMDA. Later in the wash spontaneous bursting began occurring in half of the slices that were bursting in NMDA, and the excitability of the triggered bursts increased slightly. The ability of the NMDA receptor antagonist APV to block NMDA-activated bursting was tested. Bath application of 100 or 200 microM APV alone caused little change in the normal triggered response. When 10 microM NMDA was added to the APV solution, there was little or no change in the triggered response, and no spontaneous bursting occurred. However, when 100 or 500 APV was added to the NMDA solution after NMDA burst activation had occurred, triggered bursting was reduced, but not blocked, although spontaneous bursting was blocked. In those slices that continued bursting after the washout of NMDA, bath application of 100 or 500 microM APV reduced, but did not block, triggered bursting. Spontaneous bursting continued in all slices. The ability of APV to block the induction of bursting by trains of electrical stimuli was then tested.(ABSTRACT TRUNCATED AT 400 WORDS)