Fibroblast Circadian Rhythms of PER2 Expression Depend on Membrane Potential and Intracellular Calcium

被引:30
作者
Noguchi, Takako [1 ,2 ]
Wang, Connie W. [1 ,2 ]
Pan, Haiyun [1 ,2 ,3 ]
Welsh, David K. [1 ,2 ,3 ]
机构
[1] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Ctr Chronobiol, La Jolla, CA 92093 USA
[3] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA
关键词
Calcium; Circadian rhythm; Fibroblast; Membrane potential; Potassium; SUPRACHIASMATIC NUCLEUS NEURONS; GENE-EXPRESSION; INDIVIDUAL FIBROBLASTS; REVEALS PERSISTENT; PACEMAKER NEURONS; CELL AUTONOMY; ION CHANNELS; IN-VIVO; CLOCK; TIME;
D O I
10.3109/07420528.2012.679330
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes circadian rhythms of cells and tissues throughout the body. In SCN neurons, rhythms of clock gene expression are suppressed by manipulations that hyperpolarize the plasma membrane or lower intracellular Ca2+. However, whether clocks in other cells also depend on membrane potential and calcium is unknown. In this study, the authors investigate the effects of membrane potential and intracellular calcium on circadian rhythms in mouse primary fibroblasts. Rhythms of clock gene expression were monitored using a PER2::LUC knockin reporter. Rhythms were lost or delayed at lower (hyperpolarizing) K+ concentrations. Bioluminescence imaging revealed that this loss of rhythmicity in cultures was due to loss of rhythmicity of single cells rather than loss of synchrony among cells. In lower Ca2+ concentrations, rhythms were advanced or had shorter periods. Buffering intracellular Ca2+ by the calcium chelator 1,2-Bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester (BAPTA-AM) or manipulation of inositol triphosphate (IP3)-sensitive intracellular calcium stores by thapsigargin delayed rhythms. These results suggest that the circadian clock in fibroblasts, as in SCN neurons, is regulated by membrane potential and Ca2+. Changes in intracellular Ca2+ may mediate the effects of membrane potential observed in this study. (Author correspondence: welshdk@ucsd.edu)
引用
收藏
页码:653 / 664
页数:12
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