A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability.
A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability.
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DOI：
10.1016/j.cell.2015.07.036
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发表时间：
2015-08-13
期刊：
影响因子：
64.5
通讯作者：
Allada R
中科院分区：
文献类型：
--
作者：
Flourakis M;Kula-Eversole E;Hutchison AL;Han TH;Aranda K;Moose DL;White KP;Dinner AR;Lear BC;Ren D;Diekman CO;Raman IM;Allada R
生物钟调节主起搏神经元的膜兴奋性，以控制睡眠和觉醒的日常节律。在这里，我们发现，两个明显定时的电驱动器合作，对果蝇的时钟神经元施加节奏。在早上，通过NA/NALCN离子通道的电压非依赖性钠电导使这些神经元去极化。该电流由NCA定位因子-1的节律表达驱动，将分子钟与离子通道功能联系起来。在晚上，基础钾电流达到峰值，使时钟神经元沉默。值得注意的是，钠电流和钾电流的每日反相周期也驱动小鼠时钟神经元节律。因此，我们揭示了一种进化上古老的策略，用于控制日常睡眠和觉醒的神经机制。
Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons. This current is driven by the rhythmic expression of NCA localization factor-1, linking the molecular clock to ion channel function. In the evening, basal potassium currents peak to silence clock neurons. Remarkably, daily antiphase cycles of sodium and potassium currents also drive mouse clock neuron rhythms. Thus, we reveal an evolutionarily ancient strategy for the neural mechanisms that govern daily sleep and wake.