2016
Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release
Alexandrou AJ, Brown AR, Chapman ML, Estacion M, Turner J, Mis MA, Wilbrey A, Payne EC, Gutteridge A, Cox PJ, Doyle R, Printzenhoff D, Lin Z, Marron BE, West C, Swain NA, Storer RI, Stupple PA, Castle NA, Hounshell JA, Rivara M, Randall A, Dib-Hajj SD, Krafte D, Waxman SG, Patel MK, Butt RP, Stevens EB. Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release. PLOS ONE 2016, 11: e0152405. PMID: 27050761, PMCID: PMC4822888, DOI: 10.1371/journal.pone.0152405.Peer-Reviewed Original ResearchConceptsPeripheral neuropeptide releaseSodium channel 1.7Dorsal hornPresynaptic releaseNociceptive signalingPain sensationAxonal conductionNeuropeptide releaseSpinal cordSynaptic transmissionPF-05089771Small molecule inhibitorsHuman nociceptorsAction potentialsNav1.7Nav1.7 inhibitorsUpstroke phaseHuman genetic studiesKey molecular determinantsNociceptorsSelective inhibitorMolecule inhibitorsRelative functional contributionInhibitorsFunctional contribution
2009
Maitotoxin converts the plasmalemmal Ca2+ pump into a Ca2+-permeable nonselective cation channel
Sinkins W, Estacion M, Prasad V, Goel M, Shull G, Kunze D, Schilling W. Maitotoxin converts the plasmalemmal Ca2+ pump into a Ca2+-permeable nonselective cation channel. American Journal Of Physiology - Cell Physiology 2009, 297: c1533-c1543. PMID: 19794142, PMCID: PMC2793065, DOI: 10.1152/ajpcell.00252.2009.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAnimals, Genetically ModifiedCalciumCation Transport ProteinsCationsCell MembraneCells, CulturedDown-RegulationElectric ConductivityFibroblastsHumansIon ChannelsKidneyMarine ToxinsMiceOxocinsPermeabilityPlasma Membrane Calcium-Transporting ATPasesRNA, Small InterferingSpodopteraUp-RegulationConceptsPermeable nonselective cation channelNonselective cation channelsCation channelsSpodoptera frugiperda (Sf9) insect cellsHEK cellsMouse embryonic fibroblastsHuman embryonic kidney 293 cellsEmbryonic kidney 293 cellsKidney 293 cellsInsect cellsEmbryonic fibroblastsWhole-cell membrane currentsMolecular identityCell membrane currentsCell typesPMCACytosolic freeMarine toxinsEnhanced expressionWhole-cell currentsPlasmalemmal Ca2PalytoxinATPaseCellsMaitotoxin
2004
Maitotoxin Induces Biphasic Interleukin-1β Secretion and Membrane Blebbing in Murine Macrophages
Verhoef P, Kertesy S, Estacion M, Schilling W, Dubyak G. Maitotoxin Induces Biphasic Interleukin-1β Secretion and Membrane Blebbing in Murine Macrophages. Molecular Pharmacology 2004, 66: 909-920. PMID: 15385641, DOI: 10.1124/mol.66.4.909.Peer-Reviewed Original ResearchConceptsMTX treatmentMIL-1betaIL-1betaCytolytic releaseProIL-1betaProinflammatory cytokine interleukin-1betaProinflammatory cytokine secretionCytokine interleukin-1betaMature IL-1betaMurine macrophagesInterleukin-1β secretionCytokine releaseInflammatory leukocytesCytokine secretionP2X7 receptorInterleukin-1betaInflammatory macrophagesExtracellular Ca2Extracellular glycineIntracellular Ca2Vivo responseMacrophagesCation channelsSecretionLytic phase
2003
P2X7 Receptor-Dependent Blebbing and the Activation of Rho-Effector Kinases, Caspases, and IL-1β Release
Verhoef P, Estacion M, Schilling W, Dubyak G. P2X7 Receptor-Dependent Blebbing and the Activation of Rho-Effector Kinases, Caspases, and IL-1β Release. The Journal Of Immunology 2003, 170: 5728-5738. PMID: 12759456, DOI: 10.4049/jimmunol.170.11.5728.Peer-Reviewed Original ResearchMeSH Keywords1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAdenosine TriphosphateAmidesAnimalsCaspase InhibitorsCaspasesCell LineEnzyme ActivationExtracellular SpaceHumansInterleukin-1Intracellular Signaling Peptides and ProteinsMacrophagesMiceProtein Serine-Threonine KinasesPseudopodiaPyridinesReceptors, Purinergic P2Receptors, Purinergic P2X7RhoA GTP-Binding ProteinRho-Associated KinasesSignal TransductionConceptsPlasma membrane organizationRho effector kinasesHuman embryonic kidney 293 cellsMurine macrophagesEmbryonic kidney 293 cellsPlasma membrane morphologyInhibitor KN-62Activation of RhoAKidney 293 cellsMembrane organizationTime-lapse moviesIL-1 beta releaseBlebbingKN-62Cation channel activationPore formationBiochemical analysisActivation signalsATPATP additionATP treatmentChannel activationAgonist BzATPATP concentrationCells
1997
PDGF-Stimulated Calcium Influx Changes During In Vitro Cell Transformation
Estacion M, Mordan L. PDGF-Stimulated Calcium Influx Changes During In Vitro Cell Transformation. Cellular Signalling 1997, 9: 363-366. PMID: 9376215, DOI: 10.1016/s0898-6568(96)00184-2.Peer-Reviewed Original ResearchConceptsT-type calcium channelsCalcium signalsIntracellular calcium signalsC3H 10T1/2 mouse fibroblastsCalcium channelsPreneoplastic clonesMarked reductionGrowth factorMetabolism changesVitro Cell TransformationCell transformationColonies of cellsElectrophysiology measurementsInflux changeCellsMouse fibroblasts
1996
Calcium is permeable through a maitotoxin-activated nonselective cation channel in mouse L cells
Estacion M, Nguyen H, Gargus J. Calcium is permeable through a maitotoxin-activated nonselective cation channel in mouse L cells. American Journal Of Physiology 1996, 270: c1145-c1152. PMID: 8928742, DOI: 10.1152/ajpcell.1996.270.4.c1145.Peer-Reviewed Original ResearchConceptsNonselective cation channelsCation channelsCalcium-activated potassium channelsPlatelet-derived growth factorIntracellular calciumGrowth factor responseExtracellular calciumSecondary activationPotassium channelsGrowth factorFactor responseL cellsCell typesCalciumMouse L cellsL-cell fibroblastsMouse L-cell fibroblastsCell fibroblastsCellsIrreversible opening
1993
Ca2+ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts
Wang Z, Estacion M, Mordan L. Ca2+ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts. American Journal Of Physiology 1993, 265: c1239-c1246. PMID: 8238477, DOI: 10.1152/ajpcell.1993.265.5.c1239.Peer-Reviewed Original ResearchConceptsVoltage-gated calcium channelsExtracellular calcium influxCalcium influxNordihydroguariaretic acidCalcium currentWhole-cell patch-clamp techniqueCell patch-clamp techniqueIntracellular calcium increaseInward calcium currentCell proliferationIntracellular calcium concentrationT-type channelsAddition of prostaglandinPlatelet-derived growth factorMean inhibitory dosePatch-clamp techniqueC3H/10T1/2 mouse fibroblastsInhibitory doseCalcium channelsCalcium increaseSustained increaseGrowth factorInhibitory effectCalcium concentrationCell cycle progressionCompetence induction by PDGF requires sustained calcium influx by a mechanism distinct from storage-dependent calcium influx
Estacion M, Mordan L. Competence induction by PDGF requires sustained calcium influx by a mechanism distinct from storage-dependent calcium influx. Cell Calcium 1993, 14: 439-454. PMID: 8395338, DOI: 10.1016/0143-4160(93)90003-o.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBucladesineCalciumCalcium ChannelsCell CompartmentationCell DivisionCell LineCell MembraneColforsinContact InhibitionDNA ReplicationDrug SynergismExtracellular SpaceFibroblastsGallic AcidInsulinIon Channel GatingLanthanumMiceMice, Inbred C3HNifedipinePlatelet-Derived Growth FactorS PhaseSignal TransductionTetradecanoylphorbol AcetateConceptsCalcium influxIntracellular storage sitesExtracellular calciumCalcium influx pathwaySustained calcium influxIntracellular calcium concentrationExtracellular calcium influxRelease of calciumPercentage of cellsC3H 10T1/2 mouse fibroblastsPDGF exposureSustained elevationTMB-8Influx pathwayBiphasic increaseSustained increaseDibutyryl cGMPCalcium concentrationS phasePDGFDibutyryl cAMPCell replicationSelective inhibitionReplicative competenceProgressionExpression of voltage-gated calcium channels correlates with PDGF-stimulated calcium influx and depends upon cell density in C3H 10T12 mouse fibroblasts
Estacion M, Mordan L. Expression of voltage-gated calcium channels correlates with PDGF-stimulated calcium influx and depends upon cell density in C3H 10T12 mouse fibroblasts. Cell Calcium 1993, 14: 161-171. PMID: 8384532, DOI: 10.1016/0143-4160(93)90085-k.Peer-Reviewed Original ResearchConceptsVoltage-gated calcium channelsCalcium channelsT-type voltage-gated calcium channelsWhole-cell patch-clamp recordingsWhole-cell patch-clamp techniqueCell patch-clamp techniquePatch-clamp recordingsPatch-clamp techniqueMembrane calcium channelsIntracellular calcium signalsPlasma membrane calcium channelsC3H 10T1/2 mouse fibroblastsCalcium currentCalcium influxFura-2Extracellular calciumCalcium poolSustained influxGrowth factorInflux componentFraction of cellsCalcium signalsCell densityMouse fibroblastsConfluent monolayers