Martin D, McNamara J O, Nadler J V
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
J Neurosci. 1992 May;12(5):1928-35. doi: 10.1523/JNEUROSCI.12-05-01928.1992.
Kindling is a form of experimental epileptogenesis in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. Previous studies suggested that kindling might be explained, at least in part, by an increased sensitivity of brain neurons to NMDA receptor agonists. This possibility was investigated with the use of grease-gap preparations for assaying the depolarizing responses of CA3 and CA1 hippocampal pyramidal cells to amino acid excitants. When studied 1-2 months after the last evoked seizure, CA3 pyramidal cells from kindled rats were five- to sixfold more sensitive to NMDA than CA3 pyramidal cells from controls. A similar, though smaller, effect of stimulation was observed 1 d after the last evoked seizure. The greater potency of NMDA in kindled rats can probably be explained by enhanced expression of NMDA receptors in the presence of a receptor reserve. The stimulation protocol did not alter the ability of Mg2+ to reduce NMDA potency. It also affected neither the response of CA3 pyramidal cells to AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate] nor the response of CA1 pyramidal cells to NMDA or AMPA. In area CA3, the potency of NMDA, but not of AMPA, declined 2.5-4-fold over the 1-2 month experimental period, apparently as a result of increasing age. This age-related loss of sensitivity to NMDA was completely prevented by kindling. These findings suggest that kindling prevents a loss of NMDA receptor function in CA3 pyramidal cells that normally occurs during early adulthood. Such a change could contribute to maintenance of the kindled state.
点燃效应是一种实验性癫痫发生形式，其中对脑通路进行周期性电刺激会诱导出永久性的过度兴奋状态。先前的研究表明，点燃效应至少部分可以通过脑神经元对N-甲基-D-天冬氨酸（NMDA）受体激动剂的敏感性增加来解释。使用油脂间隙制备法来测定海马CA3和CA1锥体细胞对氨基酸兴奋性递质的去极化反应，对这一可能性进行了研究。在末次诱发癫痫发作后1 - 2个月进行研究时，点燃大鼠的CA3锥体细胞对NMDA的敏感性比对对照组大鼠的CA3锥体细胞高5至6倍。在末次诱发癫痫发作后1天观察到了类似但较小的刺激效应。点燃大鼠中NMDA更强的效力可能是由于在存在受体储备的情况下NMDA受体表达增强所致。刺激方案并未改变镁离子降低NMDA效力的能力。它对CA3锥体细胞对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）的反应以及CA1锥体细胞对NMDA或AMPA的反应均无影响。在CA3区，在1 - 2个月的实验期内，NMDA而非AMPA的效力下降了2.5至4倍，这显然是由于年龄增长所致。点燃效应完全阻止了这种与年龄相关的对NMDA敏感性的丧失。这些发现表明，点燃效应可防止CA3锥体细胞中通常在成年早期发生的NMDA受体功能丧失。这样的变化可能有助于维持点燃状态。
