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Ca-\(\alpha\)1T, a fly T-type Ca2+ channel, negatively modulates sleep
  • Walton D. Jones,
  • Kyunghwa Jeong
Walton D. Jones
Korea Advanced Institute of Science and Technology - KAIST

Corresponding Author:[email protected]

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Kyunghwa Jeong
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Mammalian T-type Ca2+ channels are encoded by three separate genes (Cav3.1, 3.2, 3.3). In mammals, T-type channels are reported to be sleep stabilizers that are important in the generation of the delta rhythms of deep sleep, but controversy remains. Progress in identifying the precise physiological functions of the T-type channels has been hindered by many factors, including possible compensation between the products of these three genes and a lack of specific pharmacological inhibitors. Invertebrates have only one T-type channel gene and its physiological functions are less well-studied. We cloned Ca-\(\alpha\)1T, the only Cav3 channel gene in the Drosophila melanogaster genome, expressed it in Xenopus oocytes or HEK-293 cells, and verified that it is capable of passing typical T-type currents. Voltage-clamp analysis revealed that the biophysical properties of Ca-\(\alpha\)1T show mixed similarity, sometimes falling closer to Cav3.1, sometimes to Cav3.2, and sometimes to Cav3.3. We found that Ca-\(\alpha\)1T is broadly expressed across the adult fly brain in a pattern vaguely reminiscent of mammalian T-type channels. In addition, flies lacking Ca-\(\alpha\)1T show an abnormal increase in sleep duration that is 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.