Kyunghwa Jeong edited Introduction.tex  over 8 years ago

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Three different genes encode the pore-forming alpha subunits of mammalian T-type channels, Ca\textsubscript{v}3.1, 3.2, and 3.3. Of these, Ca\textsubscript{v}3.1 and 3.3 are highly expressed in the thalamus, where the oscillations required for NREM sleep are generated\cite{steriade:1991aa, dossi:1992aa, talley:1999aa}.  Mice lacking Ca\textsubscript{v}3.1 show reduced delta-wave activity and reduced sleep stability, suggesting that mammalian T-type currents have a sleep-promoting or stabilizing function\cite{Lee:2004ey}.  Unlike mammals, \emph{Drosophila melanogaster} has only one T-type Ca\textsuperscript{2+} channel, DmCa\textsubscript{v}3, which is also known as Dm$\alpha$G and $\alpha$1T. Ca-$\alpha$1T.  A recent study found that motor neurons in flies lacking DmCa\textsubscript{v}3 show reduced LVA but also reduced high-voltage-activated (HVA) Ca\textsuperscript{2+} currents, suggesting that although DmCa\textsubscript{v}3 seems to be a genuine T-type channel, it may have interesting biophysical properties\cite{Ryglewski:2012jk}.  We therefore cloned a single isoform of DmCa\textsubscript{v}3, expressed it in \emph{Xenopus} oocytes or HEK-293 cells, and compared its biophysical properties with those of the rat T-type channel Ca\textsubscript{v}3.1.  We also generated several DmCa\textsubscript{v}3 mutant alleles and identified a defect in their sleep/wake cycles. Contrary to results in mammals, the fly T-type Ca\textsuperscript{2+} channel destabilizes sleep.