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- Hougaard,C. etal. (2007) BrJ.Pharmacol. 151, 655.
- Chubanov,V. etal. (2012) Br.J.Pharmacol. 166, 1357.
AlomoneLabsCyPPAenhanceshSK2channelcurrentsintransientlytransfectedHEK293Tcells.Cellswerestimulatedwith100μM CyPPA (#C-110)andcurrentsweremeasuredusingwholecellvoltage-clamp.A.Timecourseat-20mVshowingtheeffectof100μMCyPPAanditsinhibitionwith150nM Apamin(#STA-200).B.Representativecurrentsatcontrolconditions(bottom)andfollowingapplicationof100μMCyPPA(top).Currentswereelicitedbya150msvoltagerampfrom-120to60mVevery10secondsfromaholdingpotentialof-80mV(currentresponsesareshownbetween-120and-10mV).Leaksweresubtractedoffline.
- 1.Kohler,M. etal. (1996) Science 273, 1709.
- 2.Stocker,M. etal. (2000) MolCellNeurosci. 15,476.
- 3.Hougaard,C. etal. (2007) BrJ.Pharmacol. 151, 655.
- 4.Seutin,V. etal. (2007) BrJ.Pharmacol. 151, 568.
- 5.Chubanov,V. etal. (2012) Br.J.Pharmacol. 166, 1357.
Ca2+-activatedpotassiumchannels(KCa)areagroupof6/7-TMionchannelsthatselectivelytransportK+ionsacrossbiologicalmembranes.Theyarebroadlyclassifiedintothreesubtypes:SK,IKandBKchannels(small,intermediateandbigconductance).
Small-conductanceCa2+-activatedK+channels(SKchannels)underliethemediumdurationafterhyperpolarizationthatfollowssingleortrainsofactionpotentialsinmanytypesofneurons.ThisfamilyiscomposedofKCa2.1(SK1),-2.2(SK2),and-2.3(SK3)isoforms,whichareexpresseddifferentiallywithinthecentralnervoussystem(CNS)1,2.
CyPPAisanactivatorofsmallconductanceKCa channelsthatdisplaysselectivityforSK2andSK3channels(EC50valuesare5.6and14µMforSK3andSK2respectivelyandefficacyis90%and71%forhSK3andhSK2,respectively)3.CyPPAdisplaysnoactivityatSK1andIK(KCa3.1)channels3.
CyPPAisatoolfordistinguishingSK2andSK3fromSK1andIK;nootheragentsdistinguishthesechannelsfromoneanother.Therefore,itenrichestherepertoireoftoolsavailabletotestthehypothesisthatSKchannelsmaybetargetsforfutureCNSdrugs4.
CyPPAwasfoundtoblockTRPM7channels,demonstratinganoverlapbetweenpharmacologicalcompoundsactingonTRPandKCachannels5.
CyPPA(#C-110) isahighlypure,synthetic,andbiologicallyactivecompound.
