TRPC 3 channels play a critical role in the theta component of pilocarpine‐induced status epilepticus in mice

Summary 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 TRPC 3 channels are effectors of the brain‐derived neurotrophic factor ( BDNF )/trkB signaling pathway. Given the long postulated role of BDNF in epileptogenesis, TRPC 3 channels may be a critical component in the underlying pathophysiology of seizure and epilepsy. In this study, we investigated the precise role of TRPC 3 channels in pilocarpine‐induced status epilepticus ( SE ). Methods The role of TRPC 3 channels was investigated using TRPC 3 knockout ( KO ) mice and TRPC 3‐selective inhibitor Pyr3. Video and electroencephalography ( EEG ) recording of pilocarpine‐induced seizures were performed. Results We found that genetic ablation of TRPC 3 channels reduces behavioral manifestations of seizures and the root‐mean‐square ( RMS ) power of SE , indicating a significant contribution of TRPC 3 channels to pilocarpine‐induced SE . Furthermore, the reduction in SE in TRPC 3 KO 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 TRPC 3 channels unequivocally contribute to pilocarpine‐induced SE and could be a novel molecular target for new anticonvulsive drugs.