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标题：Nicotine Enhances Firing Activity of Layer 5 Pyramidal Neurons in the Medial Prefrontal Cortex through Inhibition of Kv7 Channels
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作者：Shoma Izumi ; Masaki Domoto ; Hirohito Esaki 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2021
卷号：44
期号：5
页码：724-731
DOI：10.1248/bpb.b21-00137
出版社：The Pharmaceutical Society of Japan
摘要：Nicotine enhances attention, working memory and recognition. One of the brain regions associated with these effects of nicotine is the medial prefrontal cortex (mPFC). However, cellular mechanisms that induce the enhancing effects of nicotine remain unclear. To address this issue, we performed whole-cell patch-clamp recordings from mPFC layer 5 pyramidal neurons in slices of C57BL/6J mice. Shortly (approx. 2 min) after bath application of nicotine, the number of action potentials, which were elicited by depolarizing current injection, was increased, and this increase persisted for over 5 min. The effect of nicotine was blocked by the α4β2 nicotinic acetylcholine receptor (nAChR) antagonist dihydro-β-erythroidine, α7 nAChR antagonist methyllycaconitine, or intracellular perfusion with the Ca 2 chelator 1,2-bis(2-aminophenoxy)ethane- N , N , N ′, N ′-tetraacetic acid (BAPTA). Additionally, the voltage-dependent potassium 7 (Kv7) channel blocker, 10,10-bis(4-pyridinylmethyl)-9(10 H )-anthracenone dihydrochloride (XE-991), as well as nicotine, shortened the spike threshold latency and increased the spike numbers. By contrast, the Kv7 channel opener, retigabine reduced the number of firings, and the addition of nicotine did not increase the spike numbers. These results indicate that nicotine induces long-lasting enhancement of firing activity in mPFC layer 5 pyramidal neurons, which is mediated by the stimulation of the α4β2 and α7 nAChRs and subsequent increase in intracellular Ca 2 levels followed by the suppression of the Kv7 channels. The novel effect of nicotine might underlie the nicotine-induced enhancement of attention, working memory and recognition.
关键词：electrophysiology;layer 5 pyramidal neuron;nicotinic acetylcholine receptor;voltage-dependent potassium 7 channel;mouse;medial prefrontal cortex