Function of the Shaw Potassium Channel within the Drosophila Circadian Clock 英文参考文献.docVIP

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2017-05-11 发布于上海
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Function of the Shaw Potassium Channel within the Drosophila Circadian Clock 英文参考文献.doc

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Function of the Shaw Potassium Channel within the Drosophila Circadian Clock 英文参考文献

FunctionoftheShawPotassiumChannelwithinthe DrosophilaCircadianClock JamesJ.Hodge1,2*,RalfStanewsky2 1Department of Physiology and Pharmacology, School of Medical Sciences, Bristol University, Bristol, United Kingdom, 2School of Biological and Chemical Science, QueenMaryUniversityofLondon,London,UnitedKingdom Abstract Background: In addition to the molecular feedback loops, electrical activity has been shown to be important for the functionofnetworksofclockneuronsingeneratingrhythmicbehavior.Moststudieshaveusedover-expressionofforeign channelsorpharmacologicalmanipulationsthataltermembraneexcitability.Inordertodeterminethecellularmechanisms thatregulaterestingmembranepotential(RMP)inthenativeclockofDrosophilawemodulatedthefunctionofShaw,a + widelyexpressedneuronalpotassium(K )channelknowntoregulateRMPinDrosophilacentralneurons. Methodology/PrincipalFindings:WeshowthatShawisendogenouslyexpressedinclockneurons.Differentialuseofclock genepromoterswasemployedtoexpressarangeoftransgenesthateitherincreaseordecreaseShawfunctionindifferent clustersofclockneurons.UnderLDconditions,increasingShawlevelsinallclockneurons(LNv,LNd,DN1,DN2andDN3 ),or insubsetsofclockneurons(LNdandDNsorDNsalone)increaseslocomotoractivityatnight.Infree-runningconditions thesemanipulationsresultinarrhythmiclocomotoractivitywithoutdisruptionofthemolecularclock.ReducingShawinthe DNalonecausedadramaticlengtheningofthebehavioralperiod.ChangingShawlevelsinallclockneuronsalsodisrupts the rhythmic accumulation and levels of Pigment Dispersing Factor (PDF) in the dorsal projections of LNv neurons. However,changingShawlevelssolelyinLNvneuronshadlittleeffectonlocomotoractivityorrhythmicaccumulationof PDF. Conclusions/Significance:BasedonourresultsitislikelythatShawmodulatespacemakerandoutputneuronalelectrical activitythatcontrolscircadianlocomotorbehaviorbyaffectingrhythmicreleaseofPDF.Theresultssupportanimportant roleoftheDNclockneuronsinShaw-mediatedcontrolofcircadianbehavior.Inconclusion,wehavedemonstrated