Ashwood T J, Wheal H V
Department of Neurophysiology, University of Southampton.
Br J Pharmacol. 1987 Aug;91(4):815-22. doi: 10.1111/j.1476-5381.1987.tb11280.x.
1 The possible involvement of N-methyl-D-aspartate (NMDA)-receptors in epileptiform synaptic activity in the kainic acid (KA) lesioned hippocampus was investigated. In this chronic model of epilepsy there is a loss of both the early and the late components of synaptic inhibition as well as changes in the membrane properties of the surviving CA1 pyramidal cells. 2 The action of the specific NMDA-receptor antagonist D-2-amino-5-phosphonovalerate (D-APV) was tested on evoked bursts of action potentials recorded intracellularly from cells of lesioned hippocampi. The effects of D-APV on control synaptic responses from the contralateral, unlesioned hippocampi were also recorded. 3 In the presence of Mg2+ (1 mM), D-APV (20 microM) had a profound effect on the evoked epileptiform activity. Both the number of action potentials in the burst, as well as the area under the excitatory postsynaptic potential (e.p.s.p.) was considerably reduced. Furthermore this D-APV-sensitive component of the epileptiform burst had a very early onset, coincident with the first action potential in the burst. 4 D-APV (20 microM) was ineffective in blocking the e.p.s.p. evoked by Schaffer collateral afferents onto CA1 cells in slices of hippocampus contralateral to the KA lesion. 5 D-APV had no effect on the passive membrane properties of either population of cells. Hyperpolarizing potentials such as the inhibitory postsynaptic potentials (i.p.s.ps) or the afterhyperpolarization following a current-induced burst of action potentials were also unaffected. 6 It appears that an NMDA-receptor component is expressed during synaptically evoked epileptiform activity in this chronic model of epilepsy.
1 研究了N-甲基-D-天冬氨酸（NMDA）受体在 kainic 酸（KA）损伤海马体癫痫样突触活动中的可能作用。在这种慢性癫痫模型中，突触抑制的早期和晚期成分均丧失，同时存活的 CA1 锥体细胞膜特性也发生改变。2 测试了特异性 NMDA 受体拮抗剂 D-2-氨基-5-磷酸戊酸（D-APV）对从损伤海马体细胞内记录的诱发性动作电位爆发的作用。还记录了 D-APV 对来自对侧未损伤海马体的对照突触反应的影响。3 在存在 Mg2+（1 mM）的情况下，D-APV（20 microM）对诱发的癫痫样活动有深远影响。爆发中的动作电位数量以及兴奋性突触后电位（e.p.s.p.）下的面积均显著减少。此外，癫痫样爆发的这种 D-APV 敏感成分起始非常早，与爆发中的第一个动作电位同时出现。4 D-APV（20 microM）对 KA 损伤对侧海马体切片中 Schaffer 侧支传入纤维诱发的 CA1 细胞的 e.p.s.p. 无阻断作用。5 D-APV 对这两种细胞群体的被动膜特性均无影响。超极化电位，如抑制性突触后电位（i.p.s.ps）或电流诱发的动作电位爆发后的超极化后电位也未受影响。6 在这种慢性癫痫模型中，似乎在突触诱发的癫痫样活动期间表达了一种 NMDA 受体成分。
