Ca-α1T,一种果蝇T型钙离子通道,对睡眠起负向调节作用。

Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep.

作者信息

Jeong Kyunghwa, Lee Soyoung, Seo Haengsoo, Oh Yangkyun, Jang Donghoon, Choe Joonho, Kim Daesoo, Lee Jung-Ha, Jones Walton D

机构信息

KAIST, Department of Biological Sciences, Daejeon, 305-701, Republic of Korea.

Sogang University, Department of Life Sciences, Seoul, 121-742, Republic of Korea.

出版信息

Sci Rep. 2015 Dec 9;5:17893. doi: 10.1038/srep17893.

Abstract

Mammalian T-type Ca(2+) 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 Ca(2+) channels promote wakefulness rather than stabilizing sleep.

摘要

哺乳动物的T型钙通道由三个不同的基因(Cav3.1、3.2、3.3)编码。据报道,这些通道是睡眠稳定剂,对深度睡眠的δ节律的产生很重要,但仍存在争议。T型通道精确生理功能的确定至少部分受到这三个基因产物之间潜在补偿作用以及缺乏特异性药理抑制剂的阻碍。无脊椎动物只有一个T型通道基因,但其功能的研究更少。我们克隆了果蝇中唯一的Cav3通道基因Ca-α1T,将其在非洲爪蟾卵母细胞和HEK-293细胞中表达,并证实其能通过典型的T型电流。电压钳分析表明,Ca-α1T的生物物理特性呈现出混合相似性,有时更接近Cav3.1,有时接近Cav3.2,有时接近Cav3.3。我们发现Ca-α1T在成年果蝇大脑中广泛表达,其模式隐约让人联想到哺乳动物的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天睡眠时间异常增加,尽管生物钟振荡正常。因此,我们的研究表明无脊椎动物的T型钙通道促进觉醒而非稳定睡眠。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c5/4673464/ba3133bfcedc/srep17893-f1.jpg

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