Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep.
Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep.
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DOI：
10.1038/srep17893
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发表时间：
2015-12-09
影响因子：
4.6
通讯作者：
Jones WD
中科院分区：
文献类型：
--
作者：
Jeong K;Lee S;Seo H;Oh Y;Jang D;Choe J;Kim D;Lee JH;Jones WD
哺乳动物t型Ca2+通道由三个独立的基因编码（Cav3.1, 3.2, 3.3）。据报道，这些通道是睡眠稳定剂，对产生深度睡眠的δ节律很重要，但争议仍然存在。由于这三种基因产物之间的潜在补偿和缺乏特定的药理学抑制剂，对t型通道精确生理功能的鉴定至少在一定程度上受到了阻碍。无脊椎动物只有一个t型通道基因，但对其功能的研究更少。我们克隆了黑腹果蝇唯一的Cav3通道基因Ca-α1T，并在爪蟾卵母细胞和HEK-293细胞中表达，证实其通过典型的t型电流。电压箝位分析显示，Ca-α1T的生物物理性质具有混合相似性，有时更接近Cav3.1，有时更接近Cav3.2，有时更接近Cav3.3。我们发现Ca-α1T在成年果蝇大脑中广泛表达，其模式模糊地让人想起哺乳动物的t型通道。此外，缺乏Ca-α1T的果蝇在持续黑暗条件下的主观白昼表现出异常的睡眠持续时间增加，尽管生物钟正常振荡。因此，我们的研究表明，无脊椎动物的t型Ca2+通道促进觉醒，而不是稳定睡眠。
Mammalian T-type Ca2+ channels are encoded by three separate genes (Cav3.1, 3.2, 3.3). These channels are reported to be sleep stabilizers important in the generation of the delta rhythms of deep sleep, but controversy remains. The identification of precise physiological functions for the T-type channels has been hindered, at least in part, by the potential for compensation between the products of these three genes and a lack of specific pharmacological inhibitors. Invertebrates have only one T-type channel gene, but its functions are even less well-studied. We cloned Ca-α1T, the only Cav3 channel gene in Drosophila melanogaster, expressed it in Xenopus oocytes and HEK-293 cells, and confirmed it passes typical T-type currents. Voltage-clamp analysis revealed the biophysical properties of Ca-α1T show mixed similarity, sometimes falling closer to Cav3.1, sometimes to Cav3.2, and sometimes to Cav3.3. We found Ca-α1T is broadly expressed across the adult fly brain in a pattern vaguely reminiscent of mammalian T-type channels. In addition, flies lacking Ca-α1T show an abnormal increase in sleep duration most pronounced during subjective day under continuous dark conditions despite normal oscillations of the circadian clock. Thus, our study suggests invertebrate T-type Ca2+ channels promote wakefulness rather than stabilizing sleep.