TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice

PHELAN, KEVIN D.; WU, HONG; BIRNBAUMER, LUTZ; COZART, MICHAEL A.; ABRAMOWITZ, JOEL; SHWE, U THAUNG; MOCK, MATTHEW M.; ZHENG, FANG

EPILEPSIA

WILEY-BLACKWELL PUBLISHING, INC

Año: 2017 vol. 58 p. 247 - 254

0013-9580

Objective: 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 brain-derived neurotrophic factor (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). Methods: The role of TRPC3 channels was investigated using TRPC3 knockout (KO) mice and TRPC3-selective inhibitor Pyr3. Video and electroencephalography (EEG) recording of pilocarpine-induced seizures were performed. Results: 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 preictal 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. Significance: Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs.