Productcode:NMB001.Category:Mechanosensitivechannels.
AAsequence:Phe-Asn-Trp-Arg-Cys-Cys-Leu-Ile-Pro-Cys-Arg-Arg-Asn-His-Lys-Lys-Phe-Phe-Cys-NH2
Disulfidebonds:Cys5-Cys19andCys6-Cys10
Length(aa):19
Formula:C111H164N36O21S4
MolecularWeight: 2467.03Da
Appearance:Whitelyophilizedsolid
Solubility:aqueousbuffer
CASnumber:notavailable
Source:Synthetic
Purityrate:>95%
Littleisknownaboutthemolecularbasisofsomatosensorymechanotransductioninmammals.Wescreenedalibraryofpeptidetoxinsforeffectsonmechanicallyactivatedcurrentsincultureddorsalrootganglionneurons.Oneconopeptideanalogue,termed
NMB-1fornoxiousmechanosensationblocker1,selectivelyinhibits(IC501mM)sustainedmechanicallyactivatedcurrentsinasubsetofsensoryneurons.BiotinylatedNMB-1retainsactivityandbindsselectivelytoperipherinpositivenociceptivesensoryneurons.TheselectivityofNMB-1wasconfirmedbythefactthatithasnoinhibitoryeffectsonvoltage-gatedsodiumandcalciumchannels,orligand-gatedchannelssuchasacid-sensingionchannelsorTRPA1channels.Conversely,thetarantulatoxin,
GsMTx-4,whichinhibitsstretch-activatedionchannels,hadnoeffectsonmechanicallyactivatedcurrentsinsensoryneurons.Inbehavioralassays,NMB-1inhibitsresponsesonlytohighintensity,painfulmechanicalstimulationandhasnoeffectsonlowintensitymechanicalstimulationor
Thermosensation.Unexpectedly,
NMB-1wasfoundtoalsobeaninhibitorofrapidFM1-43lo
ADIng(ameasureofmechanotransduction)incochlearhaircells.Thesedatademonstratethatpharmacologicallydistinctchannelsrespondtodistincttypesofmechanicalstimuliandsuggestthatmechanicallyactivatedsustainedcurrentsunderlienoxiousmechanosensation.
NMB-1thusprovidesanoveldiagnostictoolforthemoleculardefinitionofchannelsinvolvedinhearingandpressure-evokedpain.DrewLJ.,etal.(2007)PLoSONE
Thesomatosensorysystemmediatesfundamentalphysiologicalfunctions,includingthesensesoftouch,painandproprioception.Thisvarietyoffunctionsismatchedbyadiversearrayofmechanosensoryneuronsthatrespondtoforceinaspecificfashion.Mechanotransductionbeginsatthesensorynerveendings,whichrapidlytransformmechanicalforcesintoelectricalsignals.Progresshasbeenmadeinestablishingthefunctionalpropertiesofmechanoreceptors,butithasbeenremarkablydifficulttocharacterizemechanotranducerchannelsatthemolecularlevel.However,inthepastfewyears,newfunctionalassayshaveprovidedinsightsintothebasicpropertiesandmolecularidentityofmechanotransducerchannelsinmammaliansensoryneurons.Therecentidentificationofnovelfamiliesofproteinsasmechanosensingmoleculeswillundoubtedlyaccelerateourunderstandingofmechanotransductionmechanismsinmammaliansomatosensation.DelmasP.,etal.(2011)Nature
Smartox生物素ProTx-I电压门控钠通道和T型Cav的阻断剂毒素I（ProTx-1；β-theraphotoxin-Tp1a） 是一种毒素，最初是从Prixopelma pruriens（秘鲁绿色天鹅绒狼蛛）的毒液中分离出来的。此毒素可逆地抑制抗河豚毒素（TTX）的通道 Na v 1.8（IC 50 = 27 nM）和 Na v 1.2，Na v 1.5和Na v 1.7 ，IC 50 值为50至100 nM。此外， ProTx-I 改变了T型Ca v 3.1通道的电压依赖性活动 （IC 50 = 50 nM），而不会影响灭活的电压依赖性。生物素ProTx-I是ProTx-I的生物素标签版本。
