Ding J M, Buchanan G F, Tischkau S A, Chen D, Kuriashkina L, Faiman L E, Alster J M, McPherson P S, Campbell K P, Gillette M U
Department of Cell and Structural Biology, Neuroscience Program, University of Illinois, Urbana 61801, USA.
Nature. 1998 Jul 23;394(6691):381-4. doi: 10.1038/28639.
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. Nocturnal light is the dominant regulator of this entrainment. In mammals, information about nocturnal light is transmitted by glutamate released from 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. 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.
昼夜节律时钟是复杂的生化系统，其周期约为24小时。它们整合有关太阳周期相位的时间信息，并调整自身相位，以使生物体的内部状态与当地环境的昼夜同步。夜间光线是这种同步的主要调节因素。在哺乳动物中，有关夜间光线的信息通过从视网膜投射释放到下丘脑视交叉上核中的昼夜节律时钟的谷氨酸来传递。时钟重置需要离子型谷氨酸受体的激活，该受体介导Ca2+内流。这种激活所诱导的反应取决于时钟的时间状态：在深夜早期它会延迟时钟相位，而在深夜后期时钟相位则会提前。为了研究这种差异反应，我们寻找了仅导致相位延迟的信号元件。我们分析了介导耦合Ca2+信号传导的细胞内钙通道兰尼碱受体。深夜早期细胞内Ca2+储存的耗尽阻断了谷氨酸的作用。兰尼碱受体激活剂仅在深夜早期诱导相位重置；抑制剂选择性地阻断了由光和谷氨酸诱导的延迟。这些发现表明，通过兰尼碱受体释放细胞内Ca2+参与了仅限于深夜早期的昼夜节律时钟的光诱导相位延迟。
