TY  - JOUR
AU  - Arboit, Alberto
AU  - Reboreda, Antonio
AU  - Yoshida, Motoharu
TI  - Involvement of TRPC4 and 5 Channels in Persistent Firing in Hippocampal CA1 Pyramidal Cells
JO  - Cells
VL  - 9
IS  - 2
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DZNE-2020-01099
SP  - 365
PY  - 2020
AB  - 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.
KW  - Action Potentials: drug effects
KW  - Action Potentials: physiology
KW  - Animals
KW  - Antibodies: pharmacology
KW  - Benzimidazoles: pharmacology
KW  - CA1 Region, Hippocampal: drug effects
KW  - CA1 Region, Hippocampal: physiology
KW  - Cholinergic Agonists: pharmacology
KW  - Indoles: pharmacology
KW  - Male
KW  - Mice
KW  - Neurons: drug effects
KW  - Neurons: physiology
KW  - Piperidines: pharmacology
KW  - Pyramidal Cells: drug effects
KW  - Pyramidal Cells: physiology
KW  - TRPC Cation Channels: antagonists & inhibitors
KW  - TRPC Cation Channels: metabolism
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC7072216
C6  - pmid:32033274
DO  - DOI:10.3390/cells9020365
UR  - https://pub.dzne.de/record/151515
ER  -