Department of Mechanical Engineering Sciences, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK.
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nat Commun. 2017 Dec 7;8(1):1978. doi: 10.1038/s41467-017-02161-4.
Circadian rhythms organize many aspects of cell biology and physiology to a daily temporal program that depends on clock gene expression cycles in most mammalian cell types. However, circadian rhythms are also observed in isolated mammalian red blood cells (RBCs), which lack nuclei, suggesting the existence of post-translational cellular clock mechanisms in these cells. Here we show using electrophysiological and pharmacological approaches that human RBCs display circadian regulation of membrane conductance and cytoplasmic conductivity that depends on the cycling of cytoplasmic K levels. Using pharmacological intervention and ion replacement, we show that inhibition of K transport abolishes RBC electrophysiological rhythms. Our results suggest that in the absence of conventional transcription cycles, RBCs maintain a circadian rhythm in membrane electrophysiology through dynamic regulation of K transport.
昼夜节律将细胞生物学和生理学的许多方面组织成一个依赖于大多数哺乳动物细胞类型中时钟基因表达周期的每日时间程序。然而，在没有细胞核的分离哺乳动物红细胞 (RBC) 中也观察到昼夜节律，这表明这些细胞中存在翻译后细胞时钟机制。在这里，我们使用电生理学和药理学方法表明，人类 RBC 显示出膜电导和细胞质电导率的昼夜调节，这取决于细胞质 K 水平的循环。通过药理干预和离子替代，我们表明抑制 K 转运可消除 RBC 电生理节律。我们的结果表明，在没有常规转录周期的情况下，RBC 通过 K 转运的动态调节维持膜电生理学的昼夜节律。
