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100 1 _ |a Arboit, Alberto
|0 P:(DE-2719)2811871
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245 _ _ |a Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells
260 _ _ |a Basel
|c 2020
|b MDPI
264 _ 1 |3 online
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|c 2020-02-05
336 7 _ |a article
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520 _ _ |a Persistent 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
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542 _ _ |i 2020-02-05
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|u https://creativecommons.org/licenses/by/4.0/
588 _ _ |a Dataset connected to CrossRef
650 _ 2 |a Action Potentials: drug effects
|2 MeSH
650 _ 2 |a Action Potentials: physiology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Antibodies: pharmacology
|2 MeSH
650 _ 2 |a Benzimidazoles: pharmacology
|2 MeSH
650 _ 2 |a CA1 Region, Hippocampal: drug effects
|2 MeSH
650 _ 2 |a CA1 Region, Hippocampal: physiology
|2 MeSH
650 _ 2 |a Cholinergic Agonists: pharmacology
|2 MeSH
650 _ 2 |a Indoles: pharmacology
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Neurons: drug effects
|2 MeSH
650 _ 2 |a Neurons: physiology
|2 MeSH
650 _ 2 |a Piperidines: pharmacology
|2 MeSH
650 _ 2 |a Pyramidal Cells: drug effects
|2 MeSH
650 _ 2 |a Pyramidal Cells: physiology
|2 MeSH
650 _ 2 |a TRPC Cation Channels: antagonists & inhibitors
|2 MeSH
650 _ 2 |a TRPC Cation Channels: metabolism
|2 MeSH
700 1 _ |a Reboreda, Antonio
|0 P:(DE-2719)2813728
|b 1
700 1 _ |a Yoshida, Motoharu
|0 P:(DE-2719)2811873
|b 2
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770 _ _ |a TRPC Channels
773 1 8 |a 10.3390/cells9020365
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|t Cells
|v 9
|y 2020
|x 2073-4409
773 _ _ |a 10.3390/cells9020365
|g Vol. 9, no. 2, p. 365 -
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|p 365
|t Cells
|v 9
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|x 2073-4409
856 4 _ |u https://www.mdpi.com/2073-4409/9/2/365
856 4 _ |u https://pub.dzne.de/record/151515/files/DZNE-2020-01099.pdf
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LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21