A calcium flux is required for circadian rhythm generation in mammalian pacemaker neurons
A calcium flux is required for circadian rhythm generation in mammalian pacemaker neurons
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DOI：
10.1523/jneurosci.2211-05.2005
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发表时间：
2005-08-17
影响因子：
5.3
通讯作者：
Block, GD
中科院分区：
文献类型：
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作者：
Lundkvist, GB;Kwak, Y;Block, GD
哺乳动物昼夜节律的产生涉及分子转录和翻译反馈环。目前尚不清楚膜事件如何与细胞内分子时钟相互作用，也不清楚膜活动是否参与昼夜节律的实际产生。我们研究的作用，膜电位和钙（Ca2+）内流的时钟基因周期1（Per1）的昼夜节律的表达在大鼠视交叉上核（SCN），控制昼夜节律的主起搏器。通过降低细胞外钾离子浓度或通过降低[Ca2+]阻断SCN培养物中Ca2+内流而引起的膜超极化可逆地消除了Per1的节律性表达。此外，Per1表达的幅度显着降低电压门控性钙通道拮抗剂。对于小鼠Per1和PER2观察到类似的结果。总之，这些结果强烈表明，跨膜Ca2+通量是必要的持续的分子节奏在SCN。我们建议，周期性的Ca2+内流，造成的昼夜变化的膜电位，是一个关键的过程，昼夜起搏器功能。
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.