Function of the Shaw potassium channel within the Drosophila circadian clock.
Function of the Shaw potassium channel within the Drosophila circadian clock.
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DOI：
10.1371/journal.pone.0002274
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发表时间：
2008-05-28
期刊：
影响因子：
3.7
通讯作者：
Stanewsky R
中科院分区：
文献类型：
--
作者：
Hodge JJ;Stanewsky R
除了分子反馈回路之外，电活动已经被证明对于时钟神经元网络在产生节律行为中的功能是重要的。大多数研究使用外源通道的过度表达或改变膜兴奋性的药理学操作。为了确定调节果蝇天然时钟中静息膜电位（RMP）的细胞机制，我们调节了Shaw的功能，Shaw是一种广泛表达的神经元钾（K+）通道，已知其调节果蝇中枢神经元中的RMP。我们表明，肖是内源性表达的时钟神经元。采用差异使用时钟基因启动子来表达一系列转基因，这些转基因在不同的时钟神经元簇中增加或减少Shaw功能。在LD条件下，增加所有时钟神经元（LNv、LNd、DN1、DN2和DN3）或时钟神经元子集（LNd和DNs或单独的DNs）中的Shaw水平增加夜间的运动活性。在自由运行的条件下，这些操作导致在不破坏分子钟的情况下的自发活动。仅在DN中减少Shaw就导致了行为期的显著延长。改变所有时钟神经元中的Shaw水平也会破坏LNv神经元背侧投射中色素分散因子（PDF）的节律性积累和水平。然而，仅在LNv神经元中改变Shaw水平对运动活动或PDF的节律性积累几乎没有影响。根据我们的研究结果，很可能是肖调制起搏器和输出神经元的电活动，控制昼夜运动行为的影响节奏释放的PDF。这些结果支持了DN时钟神经元在Shaw介导的昼夜节律行为控制中的重要作用。总之，我们已经证明了肖的协调和节奏的输出时钟神经元的核心作用。
In addition to the molecular feedback loops, electrical activity has been shown to be important for the function of networks of clock neurons in generating rhythmic behavior. Most studies have used over-expression of foreign channels or pharmacological manipulations that alter membrane excitability. In order to determine the cellular mechanisms that regulate resting membrane potential (RMP) in the native clock of Drosophila we modulated the function of Shaw, a widely expressed neuronal potassium (K+) channel known to regulate RMP in Drosophila central neurons. We show that Shaw is endogenously expressed in clock neurons. Differential use of clock gene promoters was employed to express a range of transgenes that either increase or decrease Shaw function in different clusters of clock neurons. Under LD conditions, increasing Shaw levels in all clock neurons (LNv, LNd, DN1, DN2 and DN3), or in subsets of clock neurons (LNd and DNs or DNs alone) increases locomotor activity at night. In free-running conditions these manipulations result in arrhythmic locomotor activity without disruption of the molecular clock. Reducing Shaw in the DN alone caused a dramatic lengthening of the behavioral period. Changing Shaw levels in all clock neurons also disrupts the rhythmic accumulation and levels of Pigment Dispersing Factor (PDF) in the dorsal projections of LNv neurons. However, changing Shaw levels solely in LNv neurons had little effect on locomotor activity or rhythmic accumulation of PDF. Based on our results it is likely that Shaw modulates pacemaker and output neuronal electrical activity that controls circadian locomotor behavior by affecting rhythmic release of PDF. The results support an important role of the DN clock neurons in Shaw-mediated control of circadian behavior. In conclusion, we have demonstrated a central role of Shaw for coordinated and rhythmic output from clock neurons.
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