FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni 英文参考文献.docVIP

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FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni 英文参考文献.doc

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FMRFamide-Like Peptides (FLPs) Enhance Voltage-Gated Calcium Currents to Elicit Muscle Contraction in the Human Parasite Schistosoma mansoni 英文参考文献

FMRFamide-LikePeptides(FLPs)EnhanceVoltage-Gated CalciumCurrentstoElicitMuscleContractioninthe HumanParasiteSchistosomamansoni EkaterinaNovozhilova1,MichaelJ.Kimber1,HaiQian1,PaulMcVeigh2,AlanP.Robertson1 ,Mostafa Zamanian1,AaronG.Maule2,TimA.Day1* 1DepartmentofBiomedicalSciencesandNeuroscienceProgram,IowaStateUniversity,Ames,Iowa,UnitedStatesofAmerica,2SchoolofBiologicalSciences,Queen’s UniversityBelfast,Belfast,NorthernIreland,UnitedKingdom Abstract Schistosomesareamongstthemostimportantandneglectedpathogensintheworld,andschistosomiasiscontrolrelies almost exclusively on a single drug. The neuromuscular system of schistosomes is fertile ground for therapeutic intervention, yet the details of physiological events involved in neuromuscular function remain largely unknown. Short amidated neuropeptides, FMRFamide-like peptides (FLPs), are distributed abundantly throughout the nervous system of every flatworm examined and they produce potent myoexcitation. Our goal here was to determine the mechanism by whichFLPselicitcontractionsofschistosomemusclefibers.ContractionstudiesshowedthattheFLPTyr-Ile-Arg-Phe-amide 2+ (YIRFamide) contracts the muscle fibers through a mechanism that requires Ca influx through sarcolemmal voltage operated Ca2+ channels (VOCCs), asthe contractions are inhibited by classical VOCC blockers nicardipine, verapamil and methoxyverapamil.Whole-cellpatch-clampexperimentsrevealedthatinwardcurrentsthroughVOCCsaresignificantlyand reversibly enhanced by the application of 1mM YIRFamide; the sustained inward currents were increased to 190% of controlsandthepeakcurrentswereincreasedto180%.InordertoexaminethebiochemicallinkbetweentheFLPreceptor and the VOCCs, PKC inhibitors calphostin C, RO 31–8220 and chelerythrine were tested and all produced concentration dependentblockofthecontractionselicitedby1mMYIRFamide.Takentogether,thedatashowthatFLPselicitcontractions 2+ byenhancingCa influxthroughVOCCcurrentsusingaPKC-dependentpathway. Citation:NovozhilovaE,