Download P194 Genetic manipulations of the NARROW ABDOMEN

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
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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
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