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Smartox/Selective blocker of SK2 (KCa2.2) channels/10TAM001-00500/0.5mg
Tamapin isapeptidetoxinisolatedfromthevenomoftheIndianredscorpionMesobuthusTamulus. Tamapin isamidatedatitsC-terminaltyrosineresidue. Tamapin bindsto smallconductanceCa2+-activatedK+ channels(SKchannels) withhighaffinityandinhibitsSKchannel-mediatedcurrentsinpyramidalneuronsofthehippocampusaswellasincelllinesexpressingdistinctSKchannelsubunits.Contraryto Apamin or Leiurotoxin-1(Scyllatoxin), Tamapin isanexcellenttoxintodiscriminateamongSKchannelsubtypesbecauseitpresentsdifferentaffinitiesfor SK1(42nM),SK2(24pM)andSK3(1.7nM) channels.ThistoxinisalsothemostpotentSK2channelblockercharacterizedsofar(IC50 forSK2channels=24pM).
Description:
AAsequence: Ala-Phe-Cys3-Asn-Leu-Arg-Arg-Cys8-Glu-Leu-Ser-Cys12-Arg-Ser-Leu-Gly-Leu-Leu-Gly-Lys-Cys21-Ile-Gly-Glu-Glu-Cys26-Lys-Cys28-Val-Pro-Tyr-NH2
Disulfidebridges: Cys3-Cys21;Cys8-Cys26;Cys12-Cys28
Length(aa): 31
Formula: C146H237N44O41S6
MolecularWeight: 3459.00Da
Appearance: Whitelyophilizedsolid
Solubility: waterandsalinebuffer
CASnumber: notavailable
Source: Synthetic
Purityrate: >97%
Reference:
SmallconductanceCa2+-activatedK+channelsastargetsofCNSdrugdevelopment
Inmostcentralneurons,smallconductanceCa(2+)-activatedK(+)channels(SKchannels)contributetoafterhyperpolarizations(AHPs),whichcontrolneuronalexcitABIlity.ThemediumAHPhaspharmacologicalpropertiessimilartorecombinantSKchannels,consistentwiththehypothesisthatSKchannelsgeneratethisafterhyperpolarizationcomponent.ItisstillunclearhowrecombinantSKchannelsarefunctionallyrelatedtotheslowAHPcomponent.ClonedSKchannelsareheteromericcomplexesofSKchannelsubunitsandcalmodulin.ThechannelsareactivatedbyCa(2+)bindingtocalmodulinthatinducesconformationalchangesresultinginchannelopening.ChanneldeactivationisthereverseprocessbroughtaboutbydissociationofCa(2+)fromcalmodulin.Inthemammalianbrain,thethreeSKchannelsubunits(SK1-3)displaypartiallyoverlappingdistributions.MostofthehigherbrainregionssuchastheneocortexandhippocampusshowexpressionofbothgenesencodingSK1andSK2channels,whereasphylogeneticallyolderbrainregionssuchasthethalamus,basalganglia,cerebellum,andbrainstemshowhighlevelsofSK3geneexpression.Atpresent,itisstillunclearwhethernativeSKchannelsaregeneratedasheteromericorhomomericchannels.Peptidetoxinssuchasapaminandscyllatoxin,aswellasorganiccompoundssuchasquaternarysaltsofbicuculline,dequalinium,UCL1684andUCL1848serveasnon-specificSKchannelblockers.TheonlyknownexceptionssofararethescorpiontoxintamapinandthepeptideinhibitorLei-Dab(7),whichbindpreferentiallytoSK2.ElectrophysiologicalandbehavioralstudiesindicatethatblockadeofSKchannelsbyapaminincreasesexcitability,lowersthethresholdfortheinductionofsynapticplasticity,andfacilitateshippocampus-dependentmemory.ThepotentialvalueofpharmacologicalSKchannelmodulationinvariouspathologicalstatessuchasincreasedepileptiformactivity,cognitiveimpairment,pain,mooddisordersandschizophreniawillbediscussed.
BlankT., etal. (2004)SmallconductanceCa2+-activatedK+channelsastargetsofCNSdrugdevelopment. CurrDrugTargetsCNSNeurolDisord. PMID: 15180477
Tamapin,avenompeptidefromtheIndianredscorpion(Mesobuthustamulus)thattargetssmallconductanceCa2+-activatedK+channelsandafterhyperpolarizationcurrentsincentralneurons
ThebiophysicalpropertiesofsmallconductanceCa(2+)-activatedK(+)(SK)channelsarewellsuitedtounderlieafterhyperpolarizations(AHPs)shapingthefiringpatternsofaconspicuousnumberofcentralandperipheralneurons.Wehaveidentifiedanewscorpiontoxin(tamapin)thatbindstoSKchannelswithhighaffinityandinhibitsSKchannel-mediatedcurrentsinpyramidalneuronsofthehippocampusaswellasincelllinesexpressingdistinctSKchannelsubunits.ThistoxindistinguishedbetweentheSKchannelsunderlyingtheapamin-sensitiveI(AHP)andtheCa(2+)-activatedK(+)channelsmediatingtheslowI(AHP)(sI(AHP))inhippocampalneurons.Comparedwithrelatedscorpiontoxins,tamapindisplayedaunique,remarkableselectivityforSK2versusSK1(approximately1750-fold)andSK3(approximately70-fold)channelsandisthemostpotentSK2channelblockercharacterizedsofar(IC(50)forSK2channels=24pm).TamapinwillfacilitatethecharacterizationofthesubunitcompositionofnativeSKchannelsandhelpdeterminetheirinvolvementinelectricalandbiochemicalsignaling.
PedarzaniP etal. (2002)Tamapin,avenompeptidefromtheIndianredscorpion(Mesobuthustamulus)thattargetssmallconductanceCa2+-activatedK+ channelsandafterhyperpolarizationcurrentsincentralneurons. J.BiolChem. PMID: 12239213
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