Ca-alpha 1T, a fly T-type Ca2+ channel, negatively modulates sleep

Abstract

Mammalian T-type Ca2+ 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-alpha 1T, 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-alpha 1T 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-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 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.