Endothelialcells(EC)formamultifunctionalsignal-transducingsurfacethatperformsdifferenttasksdependentonitslocalizationinthevesseltree.ArterialECprovideapathwayfordeliveryofoxygenfrombloodtotissue.Theymodulatethetoneofvascularsmoothmusclecells,whichinturncontrolsbloodpressureandbloodflowbyadjustingthecaliberofarteriesandarterioles.Inthemicrovascularbed,ECregulatethepermeationofvariousmetabolites,macromoleculesandgases,aswellasautocrineandparacrinefactorsandareinvolvedintheregulationofcellnutrition.Inallvesseltypes,ECareinvolvedinbloodcoagulation,controlofthetransportbetweenbloodandtissue,movementofcellsadheringtoEC,woundhealing,andangiogenesis.OtherfunctionsrequireanactiveresponseofECtovarioussignalsofmechanical,chemical,orneuronalnature.Thissignaltransductionisimpairedduringvesseldisease(arteriosclerosis)andinjury,inflammation,orhemodynamicdisturbances(hypertension).Theroleofionchannelsinthetransductionofthesesignalsintocellularresponsesisstillamatterofdebateandhasreceivedsubstantialattentiononlyinthelastfewyears.Ourcurrentknowledgeislimitedtoeffectsofionchannelsonfastendothelialresponses,thesechannelsbeingmainlyessentialfortheregulationofCa2+signaling.Hereweillustratedthenegativefeedbackofcyclicnucleotides(CNG)-inducedmembranedepolarizationonCa2+entry.Ca2+entryviareceptor-activatedcationchannels(RACC)and/orstore-operatedorcapacitative(SOC)elevates[Ca2+]iandstimulatesendothelialnitricoxidesynthase(eNOS).Thesubsequentactivationofsolubleguanylatecyclase(sGC)increasescGMP.cGMPandcAMP[viaagoNISTactivationofGprotein-coupledreceptors(GPCRs),Gs,andadenylatecyclase(AC)]activateCNGand/ornonselectivecationchannels(HCN)channels,whichinducesmembranedepolarization.ThisdepolarizationexertsanegativefeedbackonCa2+entryviaRACC/SOC.Inaddition,afeedbackinhibitionofCa2+entrychannelsviaactivationofPKGhasbeendescribed.

Contributor:KosiGramatikoff,PhD

REFERENCES:AdamsDJetal.Calciumsignallinginvascularendothelialcells:Ca2+entryandrelease.In:IonFluxinPulmonaryVascularControl,editedbyWeirEK,HumeJR,andReevesJT.NewYork:Plenum,1993,p.259-275.AokiHetal.EndothelininducestheCa2+-transientinendothelialcellsinsitu.BiochemBiophysRes.Commun181:1352-1357,1991BerridgeMJ.Capacitativecalciumentry.BiochemJ312:1-11,1995BielMetal.Cyclicnucleotidegatedchannels.AdvSecondMessengerPhosphoproteinRes33:231-250,1999BornGetal.EndotheliumandCardiovascularDisease.London:SciencePress,1998BornGVR,andSchwartzCJ.VascularEndothelium:Physiology,PathologyandTherapeutics.Stuttgart,Germany:SchatthauerVerlag,1997BussolinoFetal.Molecularmechanismsofbloodvesselformation.TrendsBiochemSci22:251-256,1997CarmelietP,andCollenD.Molecularanalysisofbloodvesselformationanddisease.AmJPhysiolHeartCircPhysiol273:H2091-H2104,1997

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