A calcium flux is required for circadian rhythm generation in mammalian pacemaker neurons

被引:144
作者
Lundkvist, GB
Kwak, Y
Davis, EK
Tei, H
Block, GD [1 ]
机构
[1] Univ Virginia, Dept Biol, Ctr Biol Timing, Charlottesville, VA 22903 USA
[2] Mitsubishi Kagaku Inst Life Sci, Res Grp Chronogenom, Machida, Tokyo 1948511, Japan
关键词
circadian rhythm; calcium; potassium; suprachiasmatic nucleus; Period; 1; PERIOD; 2;
D O I
10.1523/JNEUROSCI.2211-05.2005
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Generation of mammalian circadian rhythms involves molecular transcriptional and translational feedback loops. It is not clear how membrane events interact with the intracellular molecular clock or whether membrane activities are involved in the actual generation of the circadian rhythm. We examined the role of membrane potential and calcium (Ca2+) influx in the expression of the circadian rhythm of the clock gene Period 1 (Per1) within the rat suprachiasmatic nucleus (SCN), the master pacemaker controlling circadian rhythmicity. Membrane hyperpolarization, caused by lowering the extracellular concentration of potassium or blocking Ca2+ influx in SCN cultures by lowering [Ca2+], reversibly abolished the rhythmic expression of Per1. In addition, the amplitude of Per1 expression was markedly decreased by voltage-gated Ca2+ channel antagonists. A similar result was observed for mouse Per1 and PER2. Together, these results strongly suggest that a transmembrane Ca2+ flux is necessary for sustained molecular rhythmicity in the SCN. We propose that periodic Ca2+ influx, resulting from circadian variations in membrane potential, is a critical process for circadian pacemaker function.
引用
收藏
页码:7682 / 7686
页数:5
相关论文
共 28 条
[1]   Circadian rhythms in isolated brain regions [J].
Abe, M ;
Herzog, ED ;
Yamazaki, S ;
Straume, M ;
Tei, H ;
Sakaki, Y ;
Menaker, M ;
Block, GD .
JOURNAL OF NEUROSCIENCE, 2002, 22 (01) :350-356
[2]   Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons [J].
Aton, SJ ;
Colwell, CS ;
Harmar, AJ ;
Waschek, J ;
Herzog, ED .
NATURE NEUROSCIENCE, 2005, 8 (04) :476-483
[3]   BIOLOGICAL CLOCKS IN THE RETINA - CELLULAR MECHANISMS OF BIOLOGICAL TIMEKEEPING [J].
BLOCK, GD ;
KHALSA, SBS ;
MCMAHON, DG ;
MICHEL, S ;
GUESZ, M .
INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 146, 1993, 146 :83-144
[4]   Novel variants of voltage operated calcium channel alpha(1)-subunit transcripts in a rat liver-derived cell line: Deletion in the IVS4 voltage sensing region [J].
Brereton, HM ;
Harland, ML ;
Froscio, M ;
Petronijevic, T ;
Barritt, GJ .
CELL CALCIUM, 1997, 22 (01) :39-52
[5]   Disrupted circadian rhythms in VIP- and PHI-deficient mice [J].
Colwell, CS ;
Michel, S ;
Itri, J ;
Rodriguez, W ;
Tam, J ;
Lelievre, V ;
Hu, Z ;
Liu, X ;
Waschek, JA .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2003, 285 (05) :R939-R949
[6]   NMDA-evoked calcium transients and currents in the suprachiasmatic nucleus: gating by the circadian system [J].
Colwell, CS .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2001, 13 (07) :1420-1428
[7]   The mouse VPAC2 receptor confers suprachiasmatic nuclei cellular rhythmicity and responsiveness to vasoactive intestinal polypeptide in vitro [J].
Cutler, DJ ;
Haraura, M ;
Reed, HE ;
Shen, S ;
Sheward, WJ ;
Morrison, CF ;
Marston, HM ;
Harmar, AJ ;
Piggins, HD .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2003, 17 (02) :197-204
[8]  
DOKIM Y, 2005, EUR J NEUROSCI, V21, P1215
[9]   Molecular bases for circadian clocks [J].
Dunlap, JC .
CELL, 1999, 96 (02) :271-290
[10]   The VPAC2 receptor is essential for circadian function in the mouse suprachiasmatic nuclei [J].
Harmar, AJ ;
Marston, HM ;
Shen, SB ;
Spratt, C ;
West, KM ;
Sheward, WJ ;
Morrison, CF ;
Dorin, JR ;
Piggins, HD ;
Reubi, JC ;
Kelly, JS ;
Maywood, ES ;
Hastings, MH .
CELL, 2002, 109 (04) :497-508