Institut für Physiologie und Pathophysiologie, Philipps-Universität Marburg, Marburg, Germany.
Epilepsia. 2011 Mar;52(3):645-8. doi: 10.1111/j.1528-1167.2011.02986.x. Epub 2011 Mar 3.
In rat brain slices, the Kv channel blocker 4-aminopyridine (4-AP) induces seizure-like events. This effect is absent in slices from chronic epileptic rats generated using the kainic acid model. The reason for this phenomenon remained elusive as an altered expression level of Kv channels was ruled out as a mechanism. We recently described that the Ile400Val RNA editing of Kv1.1 generates 4-AP-insensitive Kv1 channels (Kv1.1(I400V)). We therefore hypothesized that altered RNA editing levels account for the reduced ictogenic potency of 4-AP in chronic epileptic rats. We found fourfold increased RNA editing ratios in the entorhinal cortex of chronic epileptic animals compared to healthy control animals. Electrophysiologic recordings in Xenopus oocytes revealed that the observed increased Kv1.1(I400V) editing level can in fact lead to significant loss of 4-AP sensitivity. Our data suggest that altered Kv1.1(I400V) RNA editing contributes to the reduced ictogenic potential of 4-AP in chronic epileptic rats.
在大鼠脑片中，Kv 通道阻断剂 4-氨基吡啶（4-AP）会引发类似癫痫发作的事件。使用海人酸模型生成的慢性癫痫大鼠脑片中，这种作用不存在。由于排除了 Kv 通道表达水平改变作为一种机制，因此这种现象的原因仍不清楚。我们最近描述了 Kv1.1 的 Ile400Val RNA 编辑产生 4-AP 不敏感的 Kv1 通道（Kv1.1(I400V)）。因此，我们假设 RNA 编辑水平的改变导致慢性癫痫大鼠中 4-AP 的致痫作用降低。我们发现与健康对照动物相比，慢性癫痫动物的内嗅皮层中的 RNA 编辑比率增加了四倍。在非洲爪蟾卵母细胞中的电生理记录显示，观察到的 Kv1.1(I400V)编辑水平的增加实际上可导致 4-AP 敏感性显著丧失。我们的数据表明，Kv1.1(I400V)RNA 编辑的改变导致慢性癫痫大鼠中 4-AP 的致痫潜力降低。
