Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 113-0033 Tokyo, Japan.
Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, 565-0871 Osaka, Japan.
Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9459-E9468. doi: 10.1073/pnas.1806486115. Epub 2018 Sep 17.
A primary goal of sleep research is to understand the molecular basis of sleep. Although some sleep/wake-promoting circuits and secreted substances have been identified, the detailed molecular mechanisms underlying the regulation of sleep duration have been elusive. Here, to address these mechanisms, we developed a simple computational model of a cortical neuron with five channels and a pump, which recapitulates the cortical electrophysiological characteristics of slow-wave sleep (SWS) and wakefulness. Comprehensive bifurcation and detailed mathematical analyses predicted that leak K channels play a role in generating the electrophysiological characteristics of SWS, leading to a hypothesis that leak K channels play a role in the regulation of sleep duration. To test this hypothesis experimentally, we comprehensively generated and analyzed 14 KO mice, and found that impairment of the leak K channel () decreased sleep duration. Based on these results, we hypothesize that leak K channels regulate sleep duration in mammals.
睡眠研究的主要目标之一是理解睡眠的分子基础。尽管已经确定了一些促进睡眠/觉醒的电路和分泌物质,但调节睡眠持续时间的详细分子机制仍然难以捉摸。在这里,为了解决这些机制,我们开发了一个具有五个通道和一个泵的简单皮质神经元计算模型,该模型再现了慢波睡眠(SWS)和觉醒的皮质电生理特征。综合分岔和详细的数学分析预测,泄漏钾通道在产生 SWS 的电生理特征方面发挥作用,从而提出了泄漏钾通道在调节睡眠持续时间方面发挥作用的假说。为了实验验证这一假说,我们全面生成和分析了 14 只 KO 小鼠,发现泄漏钾通道()的损伤减少了睡眠持续时间。基于这些结果,我们假设泄漏钾通道调节哺乳动物的睡眠持续时间。