ShalKv4 Channels Are Required for Maintaining Excitability during Repetitive Firing and Normal Locomotion in Drosophila 英文参考文献.docVIP

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ShalKv4 Channels Are Required for Maintaining Excitability during Repetitive Firing and Normal Locomotion in Drosophila 英文参考文献.doc

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ShalKv4 Channels Are Required for Maintaining Excitability during Repetitive Firing and Normal Locomotion in Drosophila 英文参考文献

Shal/Kv4ChannelsAreRequiredforMaintaining ExcitabilityduringRepetitiveFiringandNormal LocomotioninDrosophila YongPing.,GirmaWaro.,AshleyLicursi,SarahSmith,Dai-AnVo-Ba,SusanTsunoda* DepartmentofBiomedicalSciences,ColoradoStateUniversity,FortCollins,Colorado,UnitedStatesofAmerica Abstract Background: Rhythmic behaviors, such as walking and breathing, involve the coordinated activity of central pattern generatorsintheCNS,sensoryfeedbackfromthePNS,tomotoneuronoutputtomuscles.Unravelingtheintrinsicelectrical properties of these cellular components is essential to understanding this coordinated activity. Here, we examine the significance of the transient A-type K+ current (IA), encoded by the highly conserved Shal/Kv4 gene, in neuronal firing patterns and repetitive behaviors. While IA is present in nearly all neurons across species, elimination of IA has been complicatedinmammalsbecauseofmultiplegenesunderlyingIA,and/orelectricalremodelingthatoccursinresponseto affectingonegene. Methodology/Principal Findings: In Drosophila, the single Shal/Kv4 gene encodes the predominant IA current in many neuronalcellbodies.Usingatransgenicallyexpresseddominant-negativesubunit(DNKv4),weshowthatIAiscompletely eliminatedfromcellbodies,withnoeffectonothercurrents.Mostnotably,DNKv4neuronsdisplaymultipledefectsduring prolonged stimuli. DNKv4 neurons display shortened latency to firing, a lower threshold for repetitive firing, and a progressivedecrementinAPamplitudetoanadaptedstate.WerecordfromidentifiedmotoneuronsandshowthatShal/ Kv4channelsaresimilarlyrequiredformaintainingexcitabilityduringrepetitivefiring.Wethenexaminelarvalcrawling,and adultclimbingandgrooming,allbehaviorsthatrelyonrepetitivefiring.Weshowthatallaredefectiveintheabsenceof Shal/Kv4function.Further,knock-outofShal/Kv4functionspecificallyinmotoneuronssignificantlyaffectsthelocomotion behaviorstested. Conclusions/Significance: Based on our results, Shal/Kv4 channels regulate the initiation of firing, enable neurons to con