ω-conotoxinMVIIC(omegaconotoxinMVIIC)isaconotoxinthathasbeenisolatedfromthevenomoftheconeConusmagus. ω-conotoxinMVIIC isablockerofP/Q(IC50=35nM)andN-typecalciumchannels.ItinhibitspresynapticCa2+ channels,includingtheCa2+ channelsresponsIBLeforCa2+ uptakebyratbrainsynaptosomes,theP-typeCa2+ channelsincerebellarPurkinjecells,andasignificantfractionof ω-conotoxinGVIA-resistantcurrentsinhippocampalCA1neurons. ω-conotoxinMVIIC alsopresentsaninhibitionof ω-conotoxinGVIA-resistantdepolarization-inducedneurotransmitterreleaseincerebellarneuronsofrats.
RecentlyquotedDescription:
AAsequence: Cys1-Lys-Gly-Lys-Gly-Ala-Pro-Cys8-Arg-Lys-Thr-Met-Tyr-Asp-Cys15-Cys16-Ser-Gly-Ser-Cys20-Gly-Arg-Arg-Gly-Lys-Cys26-NH2
Disulfidebonds:Cys1-Cys16,Cys8-Cys20 andCys15-Cys26
Length(aa): 26
Formula: C106H178N40O32S7
MolecularWeight: 2750.20Da
Appearance:Whitelyophilizedsolid
Solubility: waterandsalinebuffer
CASnumber: [147794-23-8]Source: Synthetic
Purityrate: >97%
Reference:
AnewConuspeptideligandformammalianpresynapticCa2+channels
Voltage-sensitiveCa2+channelsthatcontrolneurotransmitterreleaseareblockedbyomega-conotoxin(omega-CgTx)GVIAfromthemarinesnailConusgeographus,themostwidelyusedinhibitorofneurotransmitterrelease.However,manymammaliansynapsesareomega-CgTx-GVIAinsensitive.WedescribeanewConuspeptide,omega-CgTx-MVIIC,thatisaneffectiveinhibitorofomega-CgTx-GVIA-resistantsynaptictransmission.Ca2+channeltargetsthatareinhibitedbyomega-CgTx-MVIICbutnotbyomega-CgTx-GVIAincludethosemediatingdepolarization-induced45Ca2+uptakeinratsynaptosomepreparations,“P”currentsincerebellarPurkinjecells,andasubsetofomega-CgTx-GVIA-resistantcurrentsinCA1hippocampalpyramidalcells.Thecharacterizationofomega-CgTx-MVIICbyacombinationofmoleculargeneticsandchemicalsynthesisdefinesageneralapproachforobtainingligandswithnovelreceptorsubtypespecificityfromConus.
Hillyard,D.R., etal. (1992)AnewConuspeptideligandformammalianpresynapticCa2+channels, Neuron.PMID: 1352986
Calciumchannelsubtypesinratbrain:biochemicalcharacterizationofthehigh-affinityreceptorsforomega-conopeptidesSNX-230(syntheticMVIIC),SNX-183(SVIB),andSNX-111(MVIIA)
High-thresholdvoltage-sensitivecalciumchannelsoftheN-type,L-type,andP-typehavebeendistinguishedinthemammalianCNSpredominantlyonthebasisoftheirsensitivitytoselectiveantagoNISTs.Matchingthemwithgenesidentifiedbymolecularcloningisanongoingundertaking.WhereasL-typechannelsarecharacterizedbytheirsensitivitytodihydropyridinesandP-typechannelsbysensitivitytothefunnel-webspidertoxinAgaIVA,theN-typechannelhasbeenshowntoberecognizedbytheomega-conopeptidesGVIAandMVIIA.Recently,twonewmembersofthefamilyofomega-conopeptides–MVIICfromthemarinesnailConusmagusandSVIBfromConusstriatus–havebeendescribed.Bindingandelectrophysiologicaldatasuggestthatthesetwopeptides,inadditiontointeractingwithN-typecalciumchannels,interactwithawidelydistributedreceptorinneuronalmembranesthatisdistinctfromN-typechannels.Inthisreportwedemonstratethroughbiochemicalandpharmacologicaldifferentiationatindividualreceptorpolypeptideresolution,byaffinitycross-linking,SDS-PAGE,andautorADIography,thatSNX-230(syntheticMVIIC)bindswithhighaffinitytoacalciumchannelalpha1subunitdistinctfromthehigh-affinityalpha1targetofSNX-111(syntheticMVIIA).SNX-183(syntheticSVIB)interactswithbothalpha1subunitswithloweraffinity.Whereasthealpha1subunitrecognizedwithhighaffinitybyMVIIAcorrespondstotheN-typechannel,theotherrepresentsanovelcalciumchanneldistinctfromN-,L-,andperhapsP-typechannels.
WoppmannA,(1994)Calciumchannelsubtypesinratbrain:biochemicalcharacterizationofthehigh-affinityreceptorsforomega-conopeptidesSNX-230(syntheticMVIIC),SNX-183(SVIB),andSNX-111(MVIIA), MolCellNeurosci. PMID: 7804605
Omega-conotoxinMVIICreversiblyinhibitsahumanN-typecalciumchannelandcalciuminfluxintochicksynaptosomes
Wehaveinvestigatedtheeffectsofomega-CmTXMVIIContherecombinantalpha1B-mediatedcalciumchannelexpressedinHEK293cellsandonthepredominantlyN-typecalciumchannelinchicksynaptosomes.omega-CmTXMVIICpotentlyandreversiblyinhibitedthecalciumcurrentthroughalpha1B-mediatedcalciumchannelsandinhibitedKCl-evokedincreasesin[Ca2+]iinchicksynaptosomesinaconcentration-dependentmanner.
GranthamCJ,(1994)Omega-conotoxinMVIICreversiblyinhibitsahumanN-typecalciumchannelandcalciuminfluxintochicksynaptosomes, Neuropharmacology. PMID: 8035912
