title: TRPC3 channels play a critical role in the theta component of pilocarpine-induced status epilepticus in mice.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our results demonstrate that TRPC3 channels unequivocally contribute to pilocarpine-induced SE and could be a novel molecular target for new anticonvulsive drugs.
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Phelan
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
authors.forename: U Thaung
authors.initials: UT
authors.lastname: Shwe
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cozart
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Mock
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, Durham, North Carolina, U.S.A.
authors.forename: Joel
authors.initials: J
authors.lastname: Abramowitz
authors.affiliation: Neurobiology Laboratory, National Institute of Environmental Health Sciences, Durham, North Carolina, U.S.A.|Institute of Biomedical Research (BIOMED), Catholic University of Argentina, Buenos Aires, Argentina.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, U.S.A.
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018721:Muscarinic Agonists / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D013057:Spectrum Analysis; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D013826:Theta Rhythm / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D018721:Muscarinic Agonists; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D010862:Pilocarpine
keywords: Beta rhythm; Electroencephalography; Gamma rhythm; Seizures; Spectral analysis; Transient receptor potential channels