Agrawal Newton, Alonso Angel, Ragsdale David S
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
Epilepsia. 2003 Dec;44(12):1601-4. doi: 10.1111/j.0013-9580.2003.23103.x.
Spontaneous seizures in rats emerge several weeks after induction of status epilepticus with pharmacologic treatment or electrical stimulation, providing an animal model for human temporal lobe epilepsy. In this study, we investigated whether status epilepticus caused changes in the function of voltage-gated sodium channels in entorhinal cortex layer V neurons, a cellular group important for the genesis of limbic seizures.
We induced status epilepticus in rats, by using lithium-pilocarpine, and then 2-12 weeks later, used whole-cell voltage-clamp to examine voltage-activated sodium currents of acutely dissociated layer V neurons.
Transient sodium currents of entorhinal cortex layer V neurons isolated from 9- to 12-week post-status epilepticus rats were similar to currents in age-matched controls; however, low-threshold persistent sodium currents were significantly larger. This increase in persistent activity was not seen 2-3 weeks after pilocarpine treatment; thus it occurred after a delay comparable to the delay in the appearance of spontaneous seizures.
Increased persistent currents are expected to accentuate neuronal excitability and thus may contribute to the genesis of spontaneous seizures after status epilepticus.
通过药物治疗或电刺激诱导大鼠癫痫持续状态后，数周内会出现自发性癫痫发作，这为人类颞叶癫痫提供了一种动物模型。在本研究中，我们调查了癫痫持续状态是否会导致内嗅皮层V层神经元（对边缘性癫痫发作的发生至关重要的细胞群）中电压门控钠通道功能的变化。
我们使用锂-匹罗卡品诱导大鼠癫痫持续状态，然后在2至12周后，使用全细胞膜片钳技术检测急性分离的V层神经元的电压激活钠电流。
从癫痫持续状态后9至12周的大鼠中分离出的内嗅皮层V层神经元的瞬时钠电流与年龄匹配的对照组中的电流相似；然而，低阈值持续性钠电流明显更大。在匹罗卡品治疗后2至3周未观察到这种持续性活动的增加；因此，它发生的延迟与自发性癫痫发作出现的延迟相当。
持续性电流增加预计会增强神经元兴奋性，因此可能有助于癫痫持续状态后自发性癫痫发作的发生。
