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P194 Genetic manipulations of the NARROW ABDOMEN leak channel promote unique circadian behavioral phenotypes X INGUO LU1, B ENJA MIN A LD RICH 1 , B R I DGE T LE AR 1 1 Biology, University of Iowa, Iowa City, IA, UNITED STATES The sodium leak channel NARROW ABDOMEN (NA)/ NALCN is implicated as an important determinant of membrane potential and neuronal excitability . In Drosophila, the NA channel complex functions in circadian pacemaker neuron to promote behavioral rhythmicity . To characterize functional properties of NA/NALCN channels in the circadian system, we have expressed modified versions of NA in Drosophila pacemaker neurons and assessed the effects on behavior . Drosophila NA and mammalian NALCN contain a unique ion selectivity sequence (EEKE) intermediate between that of voltage-gated calcium channels (EEEE) and voltage-gated sodium channels (DEKA) . We find that expression of a calcium-selective NA channel (EEEE) in a wild-type background mimics decreased NA function, likely acting in a dominant negative manner . In contrast, mutation of the NA ion pore (EEKE) to match a canonical sodium pore (DEKA) does not appear to disrupt channel function . While NA/NALCN orthologs in some metazoan species express both EEEE and EEKE variants, our data suggest that sodium selectivity is critical for Drosophila NA function . We have also generated a putative gain-of- function transgene (NA-GOF) based on mutations identified in C . elegans . We observe that circadian expression of NA-GOF causes distinct alterations in behavioral phase and period length . We predict that NA-GOF expression depolarizes resting membrane potential and increases neuronal excitability . Yet notably, the behavioral phenotypes observed upon expressing NA-GOF in circadian neurons differ from other manipulations known to increase excitability (NaChBac, TrpA1, dnATPase) . We are currently evaluating the impact of NA functional manipulations on neuronal activity patterns and on the molecular circadian clock . SOCie t y FOR Re Se a RCh On BiOl Og iCa l Rh y th MS 1