Mangan P S, Bertram E H
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908, U.S.A.
Neuroscience. 1997 Oct;80(4):1101-11. doi: 10.1016/s0306-4522(97)00148-6.
Intracellular recording techniques were used to examine GABA(A) receptor-mediated synaptic inhibition in pyramidal cells of the CA1 region of the rat hippocampus in the post-self sustaining limbic status epilepticus model of temporal lobe epilepsy. Orthodromically evoked, monosynaptic inhibitory postsynaptic potentials were recorded in vitro following pharmacological blockade of ionotropic glutamate and GABA(B) receptors. Inhibitory postsynaptic potentials from epileptic tissue were kinetically altered relative to controls; both the 10-90% rise-time and width (measured at half-maximum amplitude) were reduced by approximately 50% resulting in significant shortening of duration. The degree of pyramidal cell hyperexcitability, assessed before pharmacological treatment as the number of action potentials evoked by maximum intensity afferent stimulation, correlated significantly with the magnitude of synaptic potential duration reduction determined following blockade of glutamatergic neurotransmission. Bath application of the benzodiazepine type 1 receptor agonist zolpidem reduced post-self sustaining limbic status epilepticus CA1 pyramidal cell hyperexcitability substantially (but not completely) via a marked increase in inhibitory postsynaptic potential area. Post-self-sustaining limbic status epilepticus inhibitory postsynaptic potentials which exhibited the most pronounced shortening were augmented by zolpidem to a greater degree than longer duration synaptic potentials. In contrast, zolpidem-induced augmentation of control inhibitor, postsynaptic potential area was much less robust. It is suggested that a deficiency in post-self-sustaining limbic status epilepticus GABA(A) receptor-mediated synaptic inhibition contributes to a state of partial disinhibition which is a major factor in enhanced CA1 excitability in chronic limbic epilepsy. Possible mechanisms underlying post-self-sustaining limbic status epilepticus kinetic abnormalities are discussed.
在颞叶癫痫的自持续边缘性癫痫状态模型中，采用细胞内记录技术研究大鼠海马CA1区锥体细胞中GABA(A)受体介导的突触抑制。在对离子型谷氨酸和GABA(B)受体进行药理学阻断后，在体外记录了顺向诱发的单突触抑制性突触后电位。癫痫组织的抑制性突触后电位在动力学上相对于对照组发生了改变；10 - 90%上升时间和宽度（在最大振幅的一半处测量）均减少了约50%，导致持续时间显著缩短。在药物治疗前，将最大强度传入刺激诱发的动作电位数量作为锥体细胞过度兴奋性的评估指标，其与谷氨酸能神经传递阻断后确定的突触电位持续时间减少幅度显著相关。浴用苯二氮䓬1型受体激动剂唑吡坦可通过显著增加抑制性突触后电位面积，大幅（但未完全）降低自持续边缘性癫痫状态后CA1锥体细胞的过度兴奋性。唑吡坦对自持续边缘性癫痫状态后表现出最明显缩短的抑制性突触后电位的增强程度，大于对持续时间较长的突触电位的增强程度。相比之下，唑吡坦对对照抑制性突触后电位面积的增强作用则弱得多。提示自持续边缘性癫痫状态后GABA(A)受体介导的突触抑制不足导致了部分去抑制状态，这是慢性边缘性癫痫中CA1兴奋性增强的主要因素。文中还讨论了自持续边缘性癫痫状态动力学异常的可能机制。
