A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock
A neuronal ryanodine receptor mediates light-induced phase delays of the circadian clock
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DOI：
10.1038/28639
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发表时间：
1998-07-23
期刊：
影响因子：
64.8
通讯作者：
Gillette, MU
中科院分区：
文献类型：
--
作者：
Ding, JM;Buchanan, GF;Gillette, MU
生物钟是复杂的生化系统，以大约24小时为周期循环。它们整合了关于太阳周期相位的时间信息，并调整其相位，以使生物体的内部状态与当地环境昼夜同步（1，2）。夜间光线是这种夹带的主要调节器。在哺乳动物中，有关夜间光线的信息是通过视网膜投射释放的谷氨酸传递给下丘脑视交叉上核的昼夜节律钟的。时钟重置需要激活离子型谷氨酸受体，介导Ca 2+内流（3）。这种激活引起的反应取决于时钟的时间状态：在深夜，它延迟了时钟相位，而在深夜，时钟相位提前。为了研究这种差分响应，我们寻找仅对相位延迟有贡献的信号元件。我们分析了细胞内钙通道ryanodine受体，介导耦合的Ca 2+信号，细胞内Ca 2+存储在夜间早期的耗尽阻断谷氨酸的影响。Ryanodine受体的激活剂只在深夜诱导相位重置;抑制剂选择性地阻断光和谷氨酸诱导的延迟。这些发现暗示细胞内Ca 2+的释放通过兰尼碱受体在光诱导的相位延迟的昼夜节律钟限制到深夜。
Circadian clocks are complex biochemical systems that cycle with a period of approximately 24 hours. They integrate temporal information regarding phasing of the solar cycle, and adjust their phase so as to synchronize an organism's internal state to the local environmental day and night(1,2). Nocturnal light is the dominant regulator of this entrainment. In mammals, information about nocturnal light is transmitted by glutamate released om retinal projections to the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Clock resetting requires the activation of ionotropic glutamate receptors, which mediate Ca2+ influx(3). The response induced by such activation depends on the clock's temporal state: during early night it delays the clock phase, whereas in late night the clock phase is advanced. To investigate this differential response, we sought signalling elements that contribute solely to phase delay. We analysed intracellular calcium-channel ryanodine receptors, which mediate coupled Ca2+ signalling, Depletion of intracellular Ca2+ stores during early night blocked the effects of glutamate. Activators of ryanodine receptors induced phase resetting only in early night; inhibitors selectively blocked delays induced by light and glutamate. These findings implicate the release of intracellular Ca2+ through ryanodine receptors in the light-induced phase delay of the circadian clock restricted to the early night.