Kevin D Phelan1, U Thaung Shwe2, Michael A Cozart2, Hong Wu2, Matthew M Mock2, Joel Abramowitz3, Lutz Birnbaumer3,4, Fang Zheng2. 1. Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A. 2. Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A. 3. Neurobiology Laboratory, National Institute of Environmental Health Sciences, Durham, North Carolina, U.S.A. 4. Institute of Biomedical Research (BIOMED), Catholic University of Argentina, Buenos Aires, Argentina.
Abstract
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. Wiley Periodicals, Inc.
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. Wiley Periodicals, Inc.
Authors: Marie Vandecasteele; Viktor Varga; Antal Berényi; Edit Papp; Péter Barthó; Laurent Venance; Tamás F Freund; György Buzsáki Journal: Proc Natl Acad Sci U S A Date: 2014-09-02 Impact factor: 11.205
Authors: Brenda Marrero-Rosado; Marcio de Araujo Furtado; Caroline R Schultz; Michael Stone; Erica Kundrick; Katie Walker; Sean O'Brien; Fu Du; Lucille A Lumley Journal: Epilepsia Date: 2018-10-25 Impact factor: 5.864