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

• Published in: Scientific reports 2015-12, Vol.5 (1), p.17893-17893, Article 17893
• Main Authors: Jeong, Kyunghwa, Lee, Soyoung, Seo, Haengsoo, Oh, Yangkyun, Jang, Donghoon, Choe, Joonho, Kim, Daesoo, Lee, Jung-Ha, Jones, Walton D.
• Format: Article
• Language: English
• Subjects: 42/41; 631/1647/1453/1971; 631/208/1515; 631/378/1385/519; 631/378/2586; 64/24; 9/74; Animals; Brain - physiology; Calcium Channels, T-Type - genetics; Calcium Channels, T-Type - metabolism; Circadian Rhythm - genetics; Drosophila - physiology; Gene Knockdown Techniques; HEK293 Cells; Homeostasis; Humanities and Social Sciences; Humans; Membrane Potentials; multidisciplinary; Mutation; Oocytes - metabolism; Patch-Clamp Techniques; Rats; Science; Sleep - physiology; Xenopus
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep17893

Mammalian T-type Ca 2+ channels are encoded by three separate genes (Ca v 3.1, 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 Ca v 3 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 Ca v 3.1, sometimes to Ca v 3.2 and sometimes to Ca v 3.3. 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.