TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice.
TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice.
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作者：
Phelan KD;Shwe UT;Cozart MA;Wu H;Mock MM;Abramowitz J;Birnbaumer L;Zheng F
典型瞬时受体电位（TRPC）通道是一类在脑内表现出区域性和细胞特异性表达的阳离子通道。先前已经报道TRPC 3通道是BDNF/trkB信号通路的效应器。鉴于BDNF在癫痫发生中的长期假定作用，TRPC 3通道可能是癫痫发作和癫痫的基础病理生理学中的关键组分。在这项研究中，我们研究了TRPC 3通道在匹鲁卡品诱导的癫痫持续状态（SE）中的确切作用。使用TRPC 3敲除（KO）小鼠和TRPC 3选择性抑制剂Pyr 3研究TRPC 3通道的作用。对匹罗卡品诱发的癫痫发作进行视频和EEG记录。我们发现TRPC 3通道的基因消融减少了癫痫发作的行为表现和SE的均方根（RMS）功率，表明TRPC 3通道对匹鲁卡品诱导的SE有显著贡献。此外，TRPC 3 KO小鼠中SE的减少是由匹鲁卡品诱导的θ活性的选择性衰减引起的，所述θ活性主导发作前期和SE期。Pyr 3也导致了减少在整体RMS功率的匹鲁卡品诱导SE和选择性减少在SE过程中的θ活动。我们的研究结果表明，TRPC 3通道明确有助于毛果芸香碱诱导的SE，并可能成为新的抗惊厥药物的新的分子靶点。
Canonical transient receptor potential (TRPC) channels constitute a family of cation channels that exhibit a regional and cell-specific expression pattern throughout the brain. It has been reported previously that TRPC3 channels are effectors of the BDNF/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC3 channels in pilocarpine-induced Status Epilepticus (SE). The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and EEG recording of pilocarpine-induced seizures were performed. We found that genetic ablation of TRPC3 channels reduces behavioral manifestations of seizures and the root-mean-square (RMS) power of SE, indicating a significant contribution of TRPC3 channels to pilocarpine-induced SE. Furthermore, the reduction in SE in TRPC3KO mice is caused by a selective attenuation of pilocarpine-induced theta activity which dominates both the pre-ictal phase and SE phase. Pyr3 also caused a reduction in the overall RMS power of pilocarpine-induced SE and a selective reduction in the theta activity during SE. Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anti-convulsive drugs.