Food Deprivation Attenuates Seizures through CaMKII and EAG K+ Channels 英文参考文献.docVIP

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Food Deprivation Attenuates Seizures through CaMKII and EAG K+ Channels 英文参考文献.doc

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FoodDeprivationAttenuatesSeizuresthroughCaMKIIandEAGKChannels英文参考文献

FoodDeprivationAttenuatesSeizuresthrough CaMKIIandEAGKtChannels Brigitte LeBoeuf[,Todd R.Gruninger[,L.Rene Garcia* DepartmentofBiology,TexasAMUniversity,CollegeStation,Texas,UnitedStatesofAmerica Accumulated research has demonstrated the beneficial effects of dietary restriction on extending lifespan and increasingcellularstressresistance.However,reducingnutrientintakehasalsobeenshowntodirectanimalbehaviors toward food acquisition. Under food-limiting conditions, behavioral changes suggest that neuronal and muscle activities in circuits that are not involved in nutrient acquisition are down-regulated. These dietary-regulated mechanisms,ifunderstoodbetter,mightprovideanapproachtocompensatefordefectsinmoleculesthatregulate cell excitability. We previously reported that a neuromuscular circuit used in Caenorhabditis elegans male mating behavior is attenuated under food-limiting conditions. During periods between matings, sex-specific muscles that controlmovementsofthemale’scopulatoryspiculesarekeptinactivebyUNC-103ether-a-go-go–relatedgene(ERG)– likeKtchannels.Deletionofunc-103causes;30%–40%ofvirginmalestodisplaysex-muscleseizures;however,when food is deprived from males, the incidence of spontaneous muscle contractions drops to 9%–11%. In this work, we used genetics and pharmacology to address the mechanisms that act parallel with UNC-103 to suppress muscle seizuresinmalesthatlackERG-likeKtchannelfunction.Weidentifycalcium/calmodulin-dependentproteinkinaseIIas a regulator that uses different mechanisms in food and nonfood conditions to compensate for reduced ERG-like Kt channelactivity.Wefoundthatinfood-deprivedconditions,calcium/calmodulin-dependentproteinkinaseIIactscell- autonomously with ether-a-go-go Kt channels to inhibit spontaneous muscle contractions. Our work suggests that upregulatingmechanismsusedbyfooddeprivationcansuppressmuscleseizures. Citation:LeBoeufB,GruningerTR,GarciaLR(2007)FooddeprivationattenuatesseizuresthroughCaMKIIandEAGKtchannels.PLoSGen