title: Ca-α1T, a fly T-type Ca2+ channel, negatively modulates sleep.
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.
authors.affiliation: KAIST, Department of Biological Sciences, Daejeon, 305-701, Republic of Korea.
authors.forename: Kyunghwa
authors.initials: K
authors.lastname: Jeong
authors.affiliation: Sogang University, Department of Life Sciences, Seoul, 121-742, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Sogang University, Department of Life Sciences, Seoul, 121-742, Republic of Korea.
authors.forename: Haengsoo
authors.initials: H
authors.lastname: Seo
authors.affiliation: KAIST, Department of Biological Sciences, Daejeon, 305-701, Republic of Korea.
authors.forename: Yangkyun
authors.initials: Y
authors.lastname: Oh
authors.affiliation: KAIST, Department of Biological Sciences, Daejeon, 305-701, Republic of Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Jang
authors.affiliation: KAIST, Department of Biological Sciences, Daejeon, 305-701, Republic of Korea.
authors.forename: Joonho
authors.initials: J
authors.lastname: Choe
authors.affiliation: KAIST, Department of Biological Sciences, Daejeon, 305-701, Republic of Korea.
authors.forename: Daesoo
authors.initials: D
authors.lastname: Kim
authors.affiliation: Sogang University, Department of Life Sciences, Seoul, 121-742, Republic of Korea.
authors.forename: Jung-Ha
authors.initials: JH
authors.lastname: Lee
authors.affiliation: KAIST, Department of Biological Sciences, Daejeon, 305-701, Republic of Korea.
authors.forename: Walton D
authors.initials: WD
authors.lastname: Jones
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D020747:Calcium Channels, T-Type / Q000235:genetics* / Q000378:metabolism*; D002940:Circadian Rhythm / Q000235:genetics; D004330:Drosophila / Q000502:physiology*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D008564:Membrane Potentials; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D012890:Sleep / Q000502:physiology*; D014981:Xenopus
chemical_list: C500994:Cacna1g protein, rat; D020747:Calcium Channels, T-Type