BDS-1isa43aminoacidpeptidewhichwasoriginallyisolatedfromthevenomoftheseaanemonaAnemoniaViridis.BDS-1wasoriginallydescribedasahighlyselectiveblockeroftherapidlyinactivatingvoltage-gatedpotassiumchannelKv3.4/KCNC4,apotentialtherapeutictargetformajorCNSdisorders(AlzheimerandParkinsondiseases).Thetoxinactsasgatingmodifiers,mainlybyshiftingthevoltage-dependenceofactivation.Channelblockoccurswithhighaffinity(IC50of43nM)andisrapidandreversIBLe.BDS-1alsoblockstheKv3.1andKv3.2channelsalbeitwithaloweraffinity(>200nM).Finally,inamorerecentstudy,itwasdemonstratedthatBDS-1isaselectivegatingactivatoroftheNav1.7channelsubtype,animportanttargetforpainmanagement.Onthehumanisoform,modulationiswitnessedbyadrasticslowingofchannelinactivationwhichoccurswithanIC50of3nM.
Description:
AAsequence:Ala-Ala-Pro-Cys4-Phe-Cys6-Ser-Gly-Lys-Pro-Gly-Arg-Gly-Asp-Leu-Trp-Ile-Leu-Arg-Gly-Thr-Cys22-Pro-Gly-Gly-Tyr-Gly-Tyr-Thr-Ser-Asn-Cys32-Tyr-Lys-Trp-Pro-Asn-Ile-Cys39-Cys40-Tyr-Pro-His-OH
Disulfidebonds: Cys4-Cys39,Cys6-Cys32,Cys22-Cys40
Length(aa):43
Formula: C210H297N57O56S6
Appearance:Whitelyophilizedsolid
MolecularWeight:4708.37Da
CASnumber:
Source:Synthetic
Solubility:Waterorsalinebuffer
Reference:
SeaanemonepeptideswithaspecificblockingactivityagainstthefastinactivatingpotassiumchannelKv3.4
Seaanemonevenomisknowntocontaintoxinsthatareactiveonvoltage-sensitiveNa+channels,aswellasondelayedrectifierK+channelsbelongingtotheKv1family.ThisreportdescribesthepropertiesofanewsetofpeptidesfromAnemoniasulcatathatactasblockersofaspecificmemberoftheKv3potassiumchannelfamily.Thesetoxins,blooddepressingsubstance(BDS)-IandBDS-II,are43aminoacidslonganddifferatonlytwopositions.TheysharenosequencehomologieswithotherK+channeltoxinsfromseaanemones,suchasAsKS,AsKC,ShK,orBgK.InCOS-transfectedcells,theKv3.4currentwasinhibitedinareversiblemannerbyBDS-I,withanIC50valueof47nM.ThisinhibitionisspecificbecauseBDS-IfailedtoblockotherK+channelsintheKv1,Kv2,Kv3,andKv4subfamilies.InwardrectifierK+channelsarealsoinsensitivetoBDS-I.BDS-IandBDS-IIsharethesamebindingsiteonbrainsynapticmembranes,withK0.5valuesof12and19nM,respectively.WeobservedthatBDS-IandBDS-IIhavesomesequencehomologieswithotherseaanemoneNa+channelstoxins,suchasAsI,AsII,andAxI.However,theyhadaweakeffectontetrodotoxin-sensitiveNa+channelsinneuroblastomacellsandnoeffectonNa+channelsincardiacandskeletalmusclecells.BDS-IandBDS-IIarethefirstspecificblockersidentifiedsofarfortherapidlyinactivatingKv3.4channel.
Diochotetal(1998)SeaanemonepeptideswithaspecificblockingactivityagainstthefastinactivatingpotassiumchannelKv3.4.J.Biol.Chem.PMID:9506974.
Up-regulationandincreasedactivityofKV3.4channelsandtheiraccessorysubunitMinK-relatedpeptide2inducedbyamyloidpeptideareinvolvedinapoptoticneuronaldeath
TheaimofthepresentstudywastoinvestigatewhetherK(V)3.4channelsubunitsareinvolvedinneuronaldeathinducedbyneurotoxicbeta-amyloidpeptides(Abeta).Inparticular,totestthishypothesis,threemainquestionswereaddressed:1)whethertheAbetapeptidecanup-regulateboththetranscription/translationandactivityofK(V)3.4channelsubunitanditsaccessorysubunit,MinK-relatedpeptide2(MIRP2);2)whethertheincreaseinK(V)3.4expressionandactivitycanbemediatedbythenuclearfactor-kappaB(NF-kappaB)familyoftranscriptionalfactors;and3)whetherthespecificinhibitionofK(V)3.4channelsubunitrevertstheAbetapeptide-inducedneurodegenerationinhippocampalneuronsandnervegrowthfactor(NGF)-differentiatedPC-12cells.WefoundthatAbeta(1-42)treatmentinducedanincreaseinK(V)3.4andMIRP2transcriptsandproteins,detectedbyreversetranscription-polymerasechainreactionandWesternblotanalysis,respectively,inNGF-differentiatedPC-12cellsandhippocampalneurons.Patch-clampexperimentsperformedinwhole-cellconfigurationrevealedthattheAbetapeptidecausedanincreaseinI(A)currentamplitudecarriedbyK(V)3.4channelsubunits,asrevealedbytheirspecificblockadewithblooddepressingsubstance-I(BDS-I)inbothhippocampalneuronsandNGF-differentiatedPC-12cells.TheinhibitionofNF-kappaBnucleartranslocationwiththecellmembrane-permeablepeptideSN-50preventedtheincreaseinK(V)3.4proteinandtranscriptexpression.Inaddition,theSN-50peptidewasabletoblockAbeta(1-42)-inducedincreaseinK(V)3.4K(+)currentsandtopreventcelldeathcausedbyAbeta(1-42)exposure.Finally,BDS-IproducedasimilarneuroprotectiveeffectbyinhibitingtheincreaseinK(V)3.4expression.Asawhole,ourdataindicatethatK(V)3.4channelscouldbeanoveltargetforAlzheimer’sdiseasepharmacologicaltherapy.
Pannaccioneetal(2007)Up-regulationandincreasedactivityofKV3.4channelsandtheiraccessorysubunitMinK-relatedpeptide2inducedbyamyloidpeptideareinvolvedinapoptoticneuronaldeath.Mol.Pharmacol.PMID:17495071.
Voltage-dependentpotassiumcurrentsduringfastspikesofratcerebellarPurkinjeneurons:inhibitionbyBDS-Itoxin.
MartinaM.,etal.(2007)Voltage-dependentpotassiumcurrentsduringfastspikesofratcerebellarPurkinjeneurons:inhibitionbyBDS-Itoxin.J.Neurophysiol.PMID:17065256
ModulationofKv3subfamilypotassiumcurrentsbytheseaanemonetoxinBDS:significanceforCNSandbiophysicalstudies.
Kv3potassiumchannels,withtheirultra-rapidgatingandhighactivationthreshold,areessentialforhigh-frequencyfiringinmanyCNSneurons.Significantly,theKv3.4subunithasbeenimplicatedinthemajorCNSdisordersParkinson’sandAlzheimer’sdiseases,anditisclaimedthatselectivelytargetingthissubunitwillhavetherapeuticutility.PreviousworksuggestedthatBDStoxins(“blooddepressingsubstance,”fromtheseaanemoneAnemoniasulcata)werespecificblockersforrapidlyinactivatingKv3.4channels,andconsequentlythesetoxinsareincreasinglyusedasdiagnosticagentsforKv3.4subunitsincentralneurons.However,preciselyhowselectivearethesetoxinsforthisimportantCNSprotein?WeshowthatBDSisnotselectiveforKv3.4butmarkedlyinhibitscurrentthroughKv3.1andKv3.2channels.Inhibitioncomesaboutnotby“poreblock”butbystrikingmodificationofKv3gatingkineticsandvoltagedependence.ActivationandinactivationkineticsareslowedbyBDS-IandBDS-II,andV(1/2)foractivationisshiftedtomorepositivevoltages.AlaninesubstitutionmutagenesisaroundtheS3bandS4segmentsofKv3.2revealsthatBDSactsviavoltage-sensingdomains,and,consistentwiththis,ONgatingcurrentsfromnonconductingKv3.2aremarkedlyinhibited.Thealteredkineticsandgatingproperties,combinedwithlackofsubunitselectivitywithKv3subunits,seriouslyaffectstheusefulnessofBDStoxinsinCNSstudies.FurThermore,ourresultsdonoteasilyfitwiththevoltagesensor“paddle”structureproposedrecentlyforKvchannels.OurdatawillbeinformativeforexperimentsdesignedtodissectouttherolesofKv3subunitsinCNSfunctionanddysfunction.
ShukYinM.Yeung,DawnThompson,ZhurenWang,DavidFedida,BrianRobertson.ModulationofKv3subfamilypotassiumcurrentsbytheseaanemonetoxinBDS:significanceforCNSandbiophysicalstudies.TheJournalofNeuroscience25,8735-8745(2005).
ModulationofneuronalsodiumchannelsbytheseaanemonepeptideBDS-I.
Blood-depressingsubstanceI(BDS-I),a43amino-acidpeptidefromseaanemonevenom,isusedasaspecificinhibitorofKv3-familypotassiumchannels.WefoundthatBDS-Iactswithevenhigherpotencytomodulatespecifictypesofvoltage-dependentsodiumchannels.Inratdorsalrootganglion(DRG)neurons,3μMBDS-Istronglyenhancedtetrodotoxin(TTX)-sensitivesodiumcurrentbutweaklyinhibitedTTX-resistantsodiumcurrent.Inratsuperiorcervicalganglion(SCG)neurons,whichexpressonlyTTX-sensitivesodiumcurrent,BDS-Ienhancedcurrentelicitedbysmalldepolarizationsandsloweddecayofcurrentsatallvoltages(EC(50)∼300nM).BDS-IactedwithexceptionallyhighpotencyandefficacyonclonedhumanNav1.7channels,slowinginactivationby6-fold,withanEC(50)ofapproximately3nM.BDS-IalsoslowedinactivationofsodiumcurrentsinN1E-115neuroblastomacells(mainlyfromNav1.3channels),withanEC(50)∼600nM.InhippocampalCA3pyramidalneurons(mouse)andcerebellarPurkinjeneurons(mouseandrat),BDS-Ihadonlysmalleffectsoncurrentdecay(slowinginactivationby20-50%),suggestingrelativelyweaksensitivityofNav1.1andNav1.6channels.ThebiggesteffectofBDS-IincentralneuronswastoenhanceresurgentcurrentinPurkinjeneurons,aneffectreflectedinenhancementofsodiumcurrentduringtherepolarizationphaseofPurkinjeneuronactionpotentials.Overall,theseresultsshowthatBDS-Iactstomodulatesodiumchannelgatinginamannersimilartopreviouslyknownneurotoxinreceptorsite3anemonetoxinsbutwithdifferentisoformsensitivity.Mostnotably,BDS-IactswithveryhighpotencyonhumanNav1.7channels.
PinLiu,SooyeonJo,BruceP.Bean.ModulationofneuronalsodiumchannelsbytheseaanemonepeptideBDS-I.JournalofNeurophysiology107,3155-3167(2012).
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常用流动相加酸碱后PH的总结，希望大家能够提供一点自己测过的结果，谢谢先
1.直接用固体磷酸钠配制成50mM的磷酸钠溶液，再调pH到7.4；（我们试着用这个做了下，发现挂不上柱）
2.配置磷酸钠盐缓冲液：按NaH2PO4：Na2HPO4以19：81的摩尔比配制成pH7.4的缓冲液？（附一张百度出来的配方
）
3.如果是磷酸钠盐缓冲液，可以直接将50mM的NaH2PO4的水溶液用NaOH调成pH7.4吗？
再者，2和3这两个方法配制的磷酸钠盐缓冲液有什么区别？最终效果是一样的吗？如果不一样，有什么理论的知识支撑呢？个人感觉是分析化学中酸碱理论中的缓冲液那里的知识。求帮忙解答这些疑问。
另外，我还想问一下，pH对于Ni柱对His-tagged的蛋白的分离纯化影响大吗？是怎么影响的？谢谢大家了！
有了源数据之后把源数据按照大小排列，
选中源数据区域-->ALT+A1-->选中图标区右键-->更改图表类型-->散点图
因为是考察不同PH对药物的影响，样品又不好改变其PH值，这种情况怎么办？希望有经验的高手指教。
我的流动相是甲醇-水（90：10）
谢谢赐教！
请进子版按格式发贴，自行修改，谢谢。
由弱酸及其盐、弱碱及其盐组成的混合溶液，能在一定程度上抵消、减轻外加强酸或强碱对溶液酸碱度的影响，从而保持溶液的pH值相对稳定。这种溶液称为缓冲溶液。
:)
我在做一细菌不同酸碱度生长状况时,发现这些奇怪现象:pH=3的培养基灭菌(TSB液体培养基)灭菌后pH上升到到9.2!而原来pH=9.0的降到8.7(基本没多少变化),请问各位大侠,这是什么原因?
一般做不同酸碱度生长实验时,该如何才能防止pH在湿热灭菌后基本不变化?
是否可以理解为纯化水得PH范围为6.3-7.6？能否直接用pH计测量？谢谢!
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