CaMKII Is Essential for the Function of the Enteric Nervous System 英文参考文献.docVIP

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CaMKII Is Essential for the Function of the Enteric Nervous System 英文参考文献.doc

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CaMKII Is Essential for the Function of the Enteric Nervous System 英文参考文献

CaMKIIIsEssentialfortheFunctionoftheEnteric NervousSystem NaGao1.,JialieLuo1.,KarenUray2,AihuaQian1,ShijinYin1,GuoduWang3,XiyuWang3,YunXia4, JackieD.Wood3*,HongzhenHu1* 1DepartmentofIntegrativeBiologyandPharmacology,UniversityofTexasHealthScienceCenteratHouston,Houston,Texas,UnitedStatesofAmerica,2Departmentof PediatricSurgery,UniversityofTexasHealthScienceCenteratHouston,Houston,Texas,UnitedStatesofAmerica,3DepartmentofPhysiologyandCellBiology,Collegeof Medicine, The Ohio State University, Columbus, Ohio, United States of America, 4Department of Anesthesiology, College of Medicine, The Ohio State University, Columbus,Ohio,UnitedStatesofAmerica Abstract Background: Ca2+/calmodulin-dependent protein kinases (CaMKs) are major downstream mediators of neuronal calcium signaling that regulate multiple neuronal functions. CaMKII, one of the key CaMKs, plays a significant role in mediating cellularresponsestoexternalsignalingmolecules.Althoughcalciumsignalingplaysanessentialroleintheentericnervous system(ENS),theroleofCaMKIIinneurogenicintestinalfunctionhasnotbeendetermined.Inthisstudy,weinvestigated thefunctionandexpressionpatternofCaMKIIintheENSacrossseveralmammalianspecies. Methodology/PrincipalFindings:CaMKIIexpressionwascharacterizedbyimmunofluorescenceanalysesandWesternBlot. CaMKIIfunctionwasexaminedbyintracellularrecordingsandbyassaysofcoloniccontractileactivity.Immunoreactivityfor CaMKII was detected in the ENS of guinea pig, mouse, rat and human preparations. In guinea pig ENS, CaMKII immunoreactivitywasenrichedinbothnitricoxidesynthase(NOS)-andcalretinin-containingmyentericplexusneuronsand non-cholinergicsecretomotor/vasodilatorneuronsinthesubmucosalplexus.CaMKIIimmunoreactivitywasalsoexpressed inbothcholinergicandnon-cholinergicneuronsintheENSofmouse,ratandhuman.TheselectiveCaMKIIinhibitor,KN-62, suppressed stimulus-evoked purinergic slow EPSPs and ATP-induced slow EPSP-like response in guinea pig submucosal plexus, suggesting that CaMKII activity is required