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000151515 1001_ $$0P:(DE-2719)2811871$$aArboit, Alberto$$b0$$eFirst author
000151515 245__ $$aInvolvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells
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000151515 520__ $$aPersistent neural activity has been observed in vivo during working memory tasks, and supports short-term (up to tens of seconds) retention of information. While synaptic and intrinsic cellular mechanisms of persistent firing have been proposed, underlying cellular mechanisms are not yet fully understood. In vitro experiments have shown that individual neurons in the hippocampus and other working memory related areas support persistent firing through intrinsic cellular mechanisms that involve the transient receptor potential canonical (TRPC) channels. Recent behavioral studies demonstrating the involvement of TRPC channels on working memory make the hypothesis that TRPC driven persistent firing supports working memory a very attractive one. However, this view has been challenged by recent findings that persistent firing in vitro is unchanged in TRPC knock out (KO) mice. To assess the involvement of TRPC channels further, we tested novel and highly specific TRPC channel blockers in cholinergically induced persistent firing in mice CA1 pyramidal cells for the first time. The application of the TRPC4 blocker ML204, TRPC5 blocker clemizole hydrochloride, and TRPC4 and 5 blocker Pico145, all significantly inhibited persistent firing. In addition, intracellular application of TRPC4 and TRPC5 antibodies significantly reduced persistent firing. Taken together these results indicate that TRPC4 and 5 channels support persistent firing in CA1 pyramidal neurons. Finally, we discuss possible scenarios causing these controversial observations on the role of TRPC channels in persistent firing.
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000151515 650_2 $$2MeSH$$aAction Potentials: drug effects
000151515 650_2 $$2MeSH$$aAction Potentials: physiology
000151515 650_2 $$2MeSH$$aAnimals
000151515 650_2 $$2MeSH$$aAntibodies: pharmacology
000151515 650_2 $$2MeSH$$aBenzimidazoles: pharmacology
000151515 650_2 $$2MeSH$$aCA1 Region, Hippocampal: drug effects
000151515 650_2 $$2MeSH$$aCA1 Region, Hippocampal: physiology
000151515 650_2 $$2MeSH$$aCholinergic Agonists: pharmacology
000151515 650_2 $$2MeSH$$aIndoles: pharmacology
000151515 650_2 $$2MeSH$$aMale
000151515 650_2 $$2MeSH$$aMice
000151515 650_2 $$2MeSH$$aNeurons: drug effects
000151515 650_2 $$2MeSH$$aNeurons: physiology
000151515 650_2 $$2MeSH$$aPiperidines: pharmacology
000151515 650_2 $$2MeSH$$aPyramidal Cells: drug effects
000151515 650_2 $$2MeSH$$aPyramidal Cells: physiology
000151515 650_2 $$2MeSH$$aTRPC Cation Channels: antagonists & inhibitors
000151515 650_2 $$2MeSH$$aTRPC Cation Channels: metabolism
000151515 7001_ $$0P:(DE-2719)2813728$$aReboreda, Antonio$$b1
000151515 7001_ $$0P:(DE-2719)2811873$$aYoshida, Motoharu$$b2$$eLast author
000151515 770__ $$aTRPC Channels
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