2013年7月
Picrotoxin dramatically speeds the mammalian circadian clock independent of Cys-loop receptors
JOURNAL OF NEUROPHYSIOLOGY
- ,
- ,
- ,
- 巻
- 110
- 号
- 1
- 開始ページ
- 103
- 終了ページ
- 108
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1152/jn.00220.2013
- 出版者・発行元
- AMER PHYSIOLOGICAL SOC
Picrotoxin is extensively and specifically used to inhibit GABA A receptors and other members of the Cys-loop receptor superfamily. We find that picrotoxin acts independently of known Cys-loop receptors to shorten the period of the circadian clock markedly by specifically advancing the accumulation of PERIOD2 protein. We show that this mechanism is surprisingly tetrodotoxin-insensitive, and the effect is larger than any known chemical or genetic manipulation. Notably, our results indicate that the circadian target of picrotoxin is common to a variety of human and rodent cell types but not Drosophila, thereby ruling out all conserved Cys-loop receptors and known regulators of mammalian PERIOD protein stability. Given that the circadian clock modulates significant aspects of cell physiology including synaptic plasticity, these results have immediate and broad experimental implications. Furthermore, our data point to the existence of an important and novel target within the mammalian circadian timing system.
- リンク情報
- ID情報
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- DOI : 10.1152/jn.00220.2013
- ISSN : 0022-3077
- PubMed ID : 23576702
- Web of Science ID : WOS:000321197400011