Zheng Fang
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Science, Little Rock, AR, 72205, USA.
Adv Exp Med Biol. 2017;976:123-135. doi: 10.1007/978-94-024-1088-4_11.
Accumulating evidence suggest that TRPC channels play critical roles in various aspects of epileptogenesis. TRPC1/4 channels are major contributors to nonsynaptically derived epileptiform burst firing in the CA1 and the lateral septum. TRPC7 channels play a critical role in synaptically derived epileptiform burst firing. The reduction of spontaneous epileptiform bursting in the CA3 is correlated to a reduction in pilocarpine-induced SE in vivo in TRPC7 knockout mice. TRPC channels are also significant contributors to SE-induced neuronal cell death. Although the pilocarpine-induced SE itself is not significantly reduced, the SE-induced neuronal cell death is significantly reduced in the CA1 and the lateral septum, indicating that TRPC1/4 channels directly contribute to SE-induced neuronal cell death. Genetic ablation of TRPC5 also reduces SE-induced neuronal cell death in the CA1 and CA3 areas of the hippocampus.
越来越多的证据表明，瞬时受体电位通道（TRPC通道）在癫痫发生的各个方面都起着关键作用。TRPC1/4通道是CA1区和外侧隔区非突触性癫痫样爆发放电的主要促成因素。TRPC7通道在突触性癫痫样爆发放电中起关键作用。CA3区自发性癫痫样爆发的减少与TRPC7基因敲除小鼠体内毛果芸香碱诱导的癫痫持续状态（SE）的减少相关。TRPC通道也是SE诱导的神经元细胞死亡的重要促成因素。虽然毛果芸香碱诱导的SE本身没有显著减少，但CA1区和外侧隔区SE诱导的神经元细胞死亡显著减少，这表明TRPC1/4通道直接导致SE诱导的神经元细胞死亡。TRPC5的基因敲除也减少了海马CA1区和CA3区SE诱导的神经元细胞死亡。
