2023
Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Higerd-Rusli G, Tyagi S, Baker C, Liu S, Dib-Hajj F, Dib-Hajj S, Waxman S. Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2215417120. PMID: 36897973, PMCID: PMC10089179, DOI: 10.1073/pnas.2215417120.Peer-Reviewed Original ResearchConceptsCell biological mechanismsAxonal surfaceLive-cell imagingIon channel traffickingAnterograde transport vesiclesTransport vesiclesInflammatory mediatorsChannel traffickingPlasma membraneVesicular loadingIon channelsKv channelsPotential therapeutic targetPotassium channel KSodium channel NaTraffickingBiological mechanismsTherapeutic targetAbundanceRetrograde transportDistal axonsChannel NaInflammatory painNociceptor activityAxonal transportNav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons
Ghovanloo M, Effraim P, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. Nav1.7 P610T mutation in two siblings with persistent ocular pain after corneal axon transection: impaired slow inactivation and hyperexcitable trigeminal neurons. Journal Of Neurophysiology 2023, 129: 609-618. PMID: 36722722, PMCID: PMC9988530, DOI: 10.1152/jn.00457.2022.Peer-Reviewed Original ResearchConceptsPersistent ocular painTrigeminal ganglion neuronsOcular painCorneal refractive surgeryGanglion neuronsRefractive surgeryAxonal injurySlow inactivationHuman pain modelTrigeminal afferent nervesTrigeminal ganglion axonsSmall subgroupPain-related disordersEffects of injurySodium channel Nav1.7Channel slow inactivationEye painPostoperative painMost patientsPain modelAfferent nervesPersistent painTrigeminal neuronsNav1.7 mutationAxon transection
2022
The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation
Higerd-Rusli G, Tyagi S, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. The fates of internalized NaV1.7 channels in sensory neurons: Retrograde cotransport with other ion channels, axon-specific recycling, and degradation. Journal Of Biological Chemistry 2022, 299: 102816. PMID: 36539035, PMCID: PMC9843449, DOI: 10.1016/j.jbc.2022.102816.Peer-Reviewed Original ResearchConceptsMembrane proteinsIon channelsNeuronal functionDistinct neuronal compartmentsAxonal membrane proteinsRetrograde traffickingNeuronal polarityRecycling pathwayLate endosomesPlasma membraneSpecific proteinsAxonal traffickingNovel mechanismCell membraneSodium channel NaNeuronal compartmentsMultiple pathwaysLive neuronsVoltage-gated sodium channel NaProteinEndocytosisMembrane specializationsTraffickingMembraneChannel Na
2012
An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier
Gasser A, Ho TS, Cheng X, Chang KJ, Waxman SG, Rasband MN, Dib-Hajj SD. An AnkyrinG-Binding Motif Is Necessary and Sufficient for Targeting Nav1.6 Sodium Channels to Axon Initial Segments and Nodes of Ranvier. Journal Of Neuroscience 2012, 32: 7232-7243. PMID: 22623668, PMCID: PMC3413458, DOI: 10.1523/jneurosci.5434-11.2012.Peer-Reviewed Original ResearchConceptsReporter proteinAxon initial segmentKinase phosphorylation siteSodium channelsIntracellular loop 2Nodes of RanvierFull-length channelGlutamic acid residuesPhosphorylation sitesMechanism of channelVoltage-gated sodium channelsAcid residuesLoop 2Functional mouseNav1.6 sodium channelsMotifProteinVivo analysisAnkyrinGSomatodendritic compartmentCultured neuronsInitial segmentVivoAction potentialsCells
2005
Contactin regulates the current density and axonal expression of tetrodotoxin‐resistant but not tetrodotoxin‐sensitive sodium channels in DRG neurons
Rush AM, Craner MJ, Kageyama T, Dib‐Hajj S, Waxman SG, Ranscht B. Contactin regulates the current density and axonal expression of tetrodotoxin‐resistant but not tetrodotoxin‐sensitive sodium channels in DRG neurons. European Journal Of Neuroscience 2005, 22: 39-49. PMID: 16029194, DOI: 10.1111/j.1460-9568.2005.04186.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsCell Adhesion Molecules, NeuronalCell MembraneCells, CulturedContactinsDown-RegulationGanglia, SpinalMembrane PotentialsMiceMice, Inbred C57BLMice, KnockoutNAV1.8 Voltage-Gated Sodium ChannelNAV1.9 Voltage-Gated Sodium ChannelNerve Fibers, UnmyelinatedNeurons, AfferentNeuropeptidesNociceptorsPatch-Clamp TechniquesPlant LectinsSodium Channel BlockersSodium ChannelsTetrodotoxinConceptsTTX-S channelsDRG neuronsSodium channelsSmall-diameter dorsal root ganglion neuronsSmall-diameter DRG neuronsWhole-cell patch-clamp recordingsTetrodotoxin-sensitive sodium channelsDorsal root ganglion neuronsChannel isoformsNociceptive DRG neuronsTTX-sensitive sodium channelsSodium channel Nav1.2Patch-clamp recordingsSodium channel isoformsPositive neuronsGanglion neuronsSciatic nerveCell surface expressionIsolectin B4Axonal expressionUnmyelinated axonsMammalian neuronal cellsLitter matesNav1.9Neuronal cellsElectrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones
Rush AM, Dib‐Hajj S, Waxman SG. Electrophysiological properties of two axonal sodium channels, Nav1.2 and Nav1.6, expressed in mouse spinal sensory neurones. The Journal Of Physiology 2005, 564: 803-815. PMID: 15760941, PMCID: PMC1464456, DOI: 10.1113/jphysiol.2005.083089.Peer-Reviewed Original Research
2000
Localization of the tetrodotoxin-resistant sodium channel NaN in nociceptors
Fjell J, Hjelmström P, Hormuzdiar W, Milenkovic M, Aglieco F, Tyrrell L, Dib-Hajj S, Waxman S, Black J. Localization of the tetrodotoxin-resistant sodium channel NaN in nociceptors. Neuroreport 2000, 11: 199-202. PMID: 10683857, DOI: 10.1097/00001756-200001170-00039.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAxonsCorneaFemaleGanglia, SpinalImage Processing, Computer-AssistedImmunohistochemistryMolecular Sequence DataMyelin SheathNAV1.9 Voltage-Gated Sodium ChannelNerve FibersNeurons, AfferentNeuropeptidesNociceptorsPresynaptic TerminalsRanvier's NodesRatsRats, Sprague-DawleySciatic NerveSodium ChannelsTetrodotoxinConceptsSciatic nerveSmall diameter primary sensory neuronsSodium currentTetrodotoxin-resistant sodium channelsTetrodotoxin-resistant sodium currentDorsal root ganglion neuronsSodium channelsPrimary sensory neuronsAxonal sodium currentsNodes of RanvierNociceptive transmissionChannel immunoreactivityGanglion neuronsUnmyelinated fibersAxon terminalsSensory neuronsNerveImmunoreactivityAxonsNeuronsSpecific peptidesNociceptorsIB4CorneaAntibodies
1999
Sodium channels, excitability of primary sensory neurons, and the molecular basis of pain
Waxman S, Cummins T, Dib‐Hajj S, Fjell J, Black J. Sodium channels, excitability of primary sensory neurons, and the molecular basis of pain. Muscle & Nerve 1999, 22: 1177-1187. PMID: 10454712, DOI: 10.1002/(sici)1097-4598(199909)22:9<1177::aid-mus3>3.0.co;2-p.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPrimary sensory neuronsDRG neuronsSodium channel expressionSodium channel gene expressionSensory neuronsChannel gene expressionSodium channelsChannel expressionSodium currentTTX-sensitive sodium currentAbnormal burst activityNormal DRG neuronsSNS/PN3Resistant sodium currentsDistinct sodium channelsSodium channel geneChannel genesInflammatory painNerve injuryAxonal transectionElectrophysiological abnormalitiesSelective blockadePharmacological approachesBurst activityPain