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

Abstract

Mammalian T-type Ca2+ 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 Ca2+ channels promote wakefulness rather than stabilizing sleep.

Neurexin regulates nighttime sleep by modulating synaptic transmission

“…Although Ca-α1T del mutant flies exhibited increased daytime sleep compared with that of control flies (458 ± 10.8 vs. 298 ± 9.7 min), they exhibited normal nighttime sleep (538.4 ± 7.9 vs. 549.7 ± 12.3 min, Fig. 6B), consistent with a previous report40. In addition, αβ neuron-specific RNAi against cac but not Ca-α1D mimicked the defective nighttime sleep in neurexin mutant flies (Fig.…”

Transcriptome profiling of aging Drosophila photoreceptors reveals gene expression trends that correlate with visual senescence

“…In addition, ion channels, such as Sh, and genes such as Csp, Hdc and Sap47 are necessary for proper synaptic function, which is required to transmit the light signal from the retina to the brain [ 63 – 66 ]. Further, calcium-binding proteins such as Cpn function in photoreceptors to buffer potentially toxic levels of intracellular calcium induced by prolonged phototransduction [ 67 – 70 ]. Several other genes including Hexo1 , α-Man-Ia and Tsp42Ej encode proteins required for post-translational modification or degradation of Rh1 [ 71 , 72 ].…”

Evolutionary insights into T-type Ca2+ channel structure, function, and ion selectivity from the Trichoplax adhaerens homologue

“…9 A; Kang et al, 2006, 2010). The recently cloned T-type channel from Drosophila also bears a histidine in this loop (albeit 2 aa positions upstream of Ca v 3.2 His-191) and, not surprisingly, is also highly sensitive to Ni 2+ (Jeong et al, 2015). Instead, TCa v 3, mammalian Ca v 3.1 and Ca v 3.3 channels, and Lymnaea LCa v 3, all lack histidines in this region (Fig.…”