2018
Knockout of Pannexin-1 Induces Hearing Loss
Chen J, Liang C, Zong L, Zhu Y, Zhao H. Knockout of Pannexin-1 Induces Hearing Loss. International Journal Of Molecular Sciences 2018, 19: 1332. PMID: 29710868, PMCID: PMC5983795, DOI: 10.3390/ijms19051332.Peer-Reviewed Original ResearchConceptsDistortion product otoacoustic emissionsHearing lossKO miceKO mouse lineMouse linesCochlear microphonicsAuditory brainstem response thresholdActive cochlear amplificationPanx1 KO miceAuditory function testsProduct otoacoustic emissionsKnockout mouse lineFunction testsNonsyndromic hearing lossABR thresholdHearing functionHigh incidenceRecent studiesGap junctional proteinReceptor currentsOtoacoustic emissionsMiceCochlear amplificationConsistent phenotypeResponse threshold
2017
A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall
Mei L, Chen J, Zong L, Zhu Y, Liang C, Jones R, Zhao H. A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall. Neurobiology Of Disease 2017, 108: 195-203. PMID: 28823936, PMCID: PMC5675824, DOI: 10.1016/j.nbd.2017.08.002.Peer-Reviewed Original ResearchConceptsCochlear lateral wallEndocochlear potentialHearing lossGap junctional functionDeafness mechanismLateral wallHeterozygous miceCx30 mutationsHair cell degenerationHomozygous knockout miceJunctional functionHeterozygous mouse modelGap junctionsOrgan of CortiSame gap junctional plaquesEP reductionFrequent causePathological changesMouse modelKnockout miceReceptor currentsCell degenerationNormal hearingHeterozygous mutationsMiceProgressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing
Zong L, Chen J, Zhu Y, Zhao H. Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing. Biochemical And Biophysical Research Communications 2017, 489: 223-227. PMID: 28552523, PMCID: PMC5555358, DOI: 10.1016/j.bbrc.2017.05.137.Peer-Reviewed Original ResearchConceptsActive cochlear amplificationHearing lossCochlear amplificationMice ageGap junctionsAge-related hearing lossSignificant hearing lossPostnatal day 25Cochlear gap junctionsAuditory sensory hair cellsSensory hair cellsNonsyndromic hearing lossHigh incidenceOuter pillar cellsDay 25Deiters' cellsConnexin expressionHair cellsConnexin 26Outer hair cell electromotilityHair cell electromotilityPillar cellsPrevious reportsCochleaAge
2016
Expression and function of pannexins in the inner ear and hearing
Zhao H. Expression and function of pannexins in the inner ear and hearing. BMC Molecular And Cell Biology 2016, 17: 16. PMID: 27229462, PMCID: PMC4896268, DOI: 10.1186/s12860-016-0095-7.Peer-Reviewed Original ResearchConceptsFunction of pannexinsAuditory sensory hair cellsDistinct expression patternsCell apoptotic pathwaysGap junction genesSensory hair cellsGap junction proteinGene familyATP releaseExpression patternsApoptotic pathwayEndocochlear potentialJunction genesPannexinsActive cochlear amplificationPannexin expressionLateral wallCochlear lateral wallJunction proteinsOrgan of CortiHair cellsCritical roleCochlear amplificationIsoformsStria vascularis
2015
Connexin26 gap junction mediates miRNA intercellular genetic communication in the cochlea and is required for inner ear development
Zhu Y, Zong L, Mei L, Zhao H. Connexin26 gap junction mediates miRNA intercellular genetic communication in the cochlea and is required for inner ear development. Scientific Reports 2015, 5: 15647. PMID: 26490746, PMCID: PMC4614881, DOI: 10.1038/srep15647.Peer-Reviewed Original ResearchConceptsGenetic communicationOrgan developmentInner ear gap junctionsIntercellular communicationGap junctionsCochlear developmentInner ear developmentNon-coding RNAsCx26 knockout miceEar developmentGene expressionIntercellular transferCx26 deficiencyMiR-96 expressionCx30 deficiencyDevelopmental disordersPredominant isoformCell proliferationDeletionCx26Critical roleKnockout miceExpressionMiRNAsMicroRNAsPannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearing
Chen J, Zhu Y, Liang C, Chen J, Zhao H. Pannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearing. Scientific Reports 2015, 5: 10762. PMID: 26035172, PMCID: PMC4451810, DOI: 10.1038/srep10762.Peer-Reviewed Original ResearchConceptsCochlear lateral wallATP releaseHearing lossCochlear microphonicsPotential generationReceptor potentialReceptor potential generationHair cell lossLateral wallNon-junctional channelsEP generationDeficient miceCell lossEndocochlear potentialHair cellsPathological processesCochleaPhysiological conditionsJunction genesGap junction genesConnexin hemichannelsConnexin isoformsHearingDeficiencyReleasePannexin 1 deficiency can induce hearing loss
Zhao H, Zhu Y, Liang C, Chen J. Pannexin 1 deficiency can induce hearing loss. Biochemical And Biophysical Research Communications 2015, 463: 143-147. PMID: 26002464, PMCID: PMC4464954, DOI: 10.1016/j.bbrc.2015.05.049.Peer-Reviewed Original ResearchConceptsDistortion product otoacoustic emissionsHearing lossAuditory brainstem response recordingsProgressive hearing lossProduct otoacoustic emissionsHigh incidenceCell degenerationOtoacoustic emissionsGap junction proteinAcoustic stimulationCell apoptotic pathwaysHair cellsResponse recordingsGene mutationsJunction proteinsExtensive expressionCochleaActive cochlear mechanicsGap junctionsApoptotic pathwayDeficiencyHearingCritical roleCochlear mechanics
2014
Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss
Zhu Y, Chen J, Liang C, Zong L, Chen J, Jones R, Zhao H. Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss. Neuroscience 2014, 284: 719-729. PMID: 25451287, PMCID: PMC4268423, DOI: 10.1016/j.neuroscience.2014.10.061.Peer-Reviewed Original ResearchConceptsLate-onset hearing lossActive cochlear amplificationDistortion product otoacoustic emissionsHearing lossNonsyndromic hearing lossTherapeutic interventionsProgressive hearing lossHair cell lossPostnatal day 5Cochlear amplificationProduct otoacoustic emissionsConditional knockout miceKnockout miceClinical observationsDay 5Cell lossEndocochlear potentialOtoacoustic emissionsNormal hearingCx26 expressionDeafness mechanismMiceCx26 deficiencyCochleaInterventionDeafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders
Chen J, Chen J, Zhu Y, Liang C, Zhao H. Deafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders. Biochemical And Biophysical Research Communications 2014, 448: 28-32. PMID: 24732355, PMCID: PMC4105360, DOI: 10.1016/j.bbrc.2014.04.016.Peer-Reviewed Original ResearchConceptsAuditory brainstem responseHair cell degenerationKO miceCongenital deafnessEP reductionEndocochlear potentialHearing lossCell degenerationDevelopmental disordersActive cochlear amplificationCx26 knockout miceComplete hearing lossCx26 deficiencyPostnatal day 5Connexin 26 mutationsNonsyndromic hearing lossBrainstem responseMouse modelKnockout miceDay 5Deafness mechanismMajor causeMiceDeafnessDisordersThe role of an inwardly rectifying K+ channel (Kir4.1) in the inner ear and hearing loss
Chen J, Zhao H. The role of an inwardly rectifying K+ channel (Kir4.1) in the inner ear and hearing loss. Neuroscience 2014, 265: 137-146. PMID: 24480364, PMCID: PMC4007161, DOI: 10.1016/j.neuroscience.2014.01.036.Peer-Reviewed Original ResearchConceptsInner earGanglion neuronsHearing lossSpiral ganglion neuron degenerationPotassium channelsSatellite glial cellsSpiral ganglion neuronsKir4.1 potassium channelsPathogenesis of deafnessPotassium channel functionNeuron degenerationSeSAME syndromeFunctional impairmentGlial cellsCochlear ganglionTherapeutic strategiesKir4.1 channelsCochlear developmentStria vascularisKir4.1 subunitKir4.1Scala mediaIntermediate cellsAbsence of EpEar
2012
Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss
Liang C, Zhu Y, Zong L, Lu G, Zhao H. Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss. Neuroscience Letters 2012, 528: 36-41. PMID: 22975134, PMCID: PMC3467974, DOI: 10.1016/j.neulet.2012.08.085.Peer-Reviewed Original ResearchConceptsHair cell lossAuditory brainstem responseCell degenerationCell lossNeuron degenerationPostnatal developmentCx26 deficiencyCochlear hair cell lossSpiral ganglion neuron degenerationDevelopment disordersCx26 knockout miceHair cellsHair cell functionOuter hair cellsSG neuronsNonsyndromic hearing lossKO miceBrainstem responseCochlear cellsHearing lossBasal turnMouse modelKnockout miceCongenital deafnessSignificant degenerationATP activates P2X receptors to mediate gap junctional coupling in the cochlea
Zhu Y, Zhao H. ATP activates P2X receptors to mediate gap junctional coupling in the cochlea. Biochemical And Biophysical Research Communications 2012, 426: 528-532. PMID: 22982314, PMCID: PMC3471361, DOI: 10.1016/j.bbrc.2012.08.119.Peer-Reviewed Original ResearchConceptsP2X receptorsGap junctional couplingCochlear gap junctionsP2Y receptor agonist UTPGap junctionsJunctional couplingP2X receptor antagonistMetabotropic purinergic receptorsReceptor agonist UTPStimulation of ATPPhysiological levelsReceptor antagonistP2Y receptorsPurinergic controlPurinergic receptorsBenzoylbenzoyl-ATPNoise stressReceptorsIonic homeostasisCochleaDisulfonic acidCritical roleIntercellular channelsATPCells
2009
Modulation of Outer Hair Cell Electromotility by Cochlear Supporting Cells and Gap Junctions
Yu N, Zhao H. Modulation of Outer Hair Cell Electromotility by Cochlear Supporting Cells and Gap Junctions. PLOS ONE 2009, 4: e7923. PMID: 19936276, PMCID: PMC2775161, DOI: 10.1371/journal.pone.0007923.Peer-Reviewed Original Research
2008
Identification and characterization of pannexin expression in the mammalian cochlea
Wang X, Streeter M, Liu Y, Zhao H. Identification and characterization of pannexin expression in the mammalian cochlea. The Journal Of Comparative Neurology 2008, 512: 336-346. PMID: 19009624, PMCID: PMC2630187, DOI: 10.1002/cne.21898.Peer-Reviewed Original ResearchConceptsSpiral ganglion neuronsCochlear lateral wallDiffuse cytoplasmic labelingMammalian cochleaType II fibrocytesOrgan of CortiBlood vessel cellsOuter sulcus cellsWestern blot analysisDistinct cellular distributionGanglion neuronsPolymerase chain reactionGap junctional proteinRat cochleaInterdental cellsStria vascularisPunctate labelingDeiters' cellsSpiral limbusImmunofluorescent stainingCochlear boneHair cellsBasal cellsSpiral prominencePannexin expressionHemichannel-Mediated Inositol 1,4,5-Trisphosphate (IP3) Release in the Cochlea: A Novel Mechanism of IP3 Intercellular Signaling
Gossman D, Zhao H. Hemichannel-Mediated Inositol 1,4,5-Trisphosphate (IP3) Release in the Cochlea: A Novel Mechanism of IP3 Intercellular Signaling. Cell Communication & Adhesion 2008, 15: 305-315. PMID: 18979296, PMCID: PMC5543712, DOI: 10.1080/15419060802357217.Peer-Reviewed Original ResearchConceptsIntercellular signalingLong-distance intercellular communicationImportant second messengerGap junction channelsGap junction hemichannel blockerGap junction hemichannelsCochlear sensory epitheliumCassette transportersSecond messengerIntercellular communicationDeafness mutantsJunction channelsCell surfaceExtracellular mediatorsSignalingNovel mechanismSensory epitheliumHemichannelsExtracellular pathwaysTrisphosphateInositolFluorescence polarization techniqueHemichannel blockersImportant roleExtracellular application
2006
Gap Junctions and Cochlear Homeostasis
Zhao H, Kikuchi T, Ngezahayo A, White T. Gap Junctions and Cochlear Homeostasis. The Journal Of Membrane Biology 2006, 209: 177. PMID: 16773501, PMCID: PMC1609193, DOI: 10.1007/s00232-005-0832-x.Peer-Reviewed Original ResearchConceptsGap junction systemConnexin mutationsHuman deafnessConnective tissue cell gap junction systemEpithelial cell gap junction systemGap junctionsMammalian inner earNon-sensory cellsGap junction networkGap junction functionConnexin genesTransduction processesDifferent connexinsFunctional studiesMutant channelsHereditary deafnessJunction functionSensory cellsCochlear homeostasisMutationsRecycling mechanismCritical roleConnexinsHigh incidenceAnimal models
2005
Connexin26 is responsible for anionic molecule permeability in the cochlea for intercellular signalling and metabolic communications
Zhao H. Connexin26 is responsible for anionic molecule permeability in the cochlea for intercellular signalling and metabolic communications. European Journal Of Neuroscience 2005, 21: 1859-1868. PMID: 15869481, PMCID: PMC2548270, DOI: 10.1111/j.1460-9568.2005.04031.x.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAffinity LabelsAnimalsAnionsAnti-Inflammatory AgentsCalciumCationsCell CommunicationCell CountCell Membrane PermeabilityCells, CulturedCochleaConnexin 26ConnexinsDose-Response Relationship, DrugEnzyme InhibitorsFluorescent DyesGap JunctionsGlycyrrhetinic AcidGuinea PigsIntracellular MembranesPlatelet Aggregation InhibitorsProadifenPyridoxal PhosphateSpectrometry, FluorescenceTime FactorsConceptsCharge selectivityLarge pore sizeCationic fluorescent dyeIntercellular signalingAnionic dyesDye sizeGap junctionsMetabolic communicationPore sizeMolecule permeabilityMolecular permeabilitySelectivityEnergy moleculesCationic probePassage of ionsFluorescent dyeGap junctional permeabilityMoleculesCochlear sensory epitheliumDyeCochlear gap junctions
2004
Paradoxical Enhancement of Active Cochlear Mechanics in Long-Term Administration of Salicylate
Huang Z, Luo Y, Wu Z, Tao Z, Jones R, Zhao H. Paradoxical Enhancement of Active Cochlear Mechanics in Long-Term Administration of Salicylate. Journal Of Neurophysiology 2004, 93: 2053-2061. PMID: 15590729, DOI: 10.1152/jn.00959.2004.Peer-Reviewed Original ResearchConceptsDistortion product otoacoustic emissionsLong-term administrationOtotoxic mechanismsLong-term salicylate administrationAwake guinea pigsReversible hearing lossSalicylate-induced tinnitusActive cochlear mechanicsProduct otoacoustic emissionsInitial normal levelsDistortion productsSalicylate administrationSodium salicylateDaily injectionsSaline injectionHearing functionHearing lossCubic distortion productSingle injectionControl animalsOHC levelsCommon drugsSalicylate treatmentAcoustic emissionRate of recovery
2001
Long-term natural culture of cochlear sensory epithelia of guinea pigs
Zhao H. Long-term natural culture of cochlear sensory epithelia of guinea pigs. Neuroscience Letters 2001, 315: 73-76. PMID: 11711218, DOI: 10.1016/s0304-3940(01)02357-6.Peer-Reviewed Original ResearchConceptsCochlear sensory epitheliumCochlear sensory epithelial cellsSensory epithelial cellsSensory epitheliumHair cell markersCochlear cell lineIsolated cell clonesCochlear cellsEpithelial morphotypeGenetic manipulationProtein ZO-1Genetic studiesValuable cell sourceCulture cellsGuinea pigsCell linesEpithelial cellsZO-1Tight junctionsCell markersNatural cultureCell sourceCellsCell clonesCulture mediumChlorpromazine Alters Outer Hair Cell Electromotility
Lue A, Zhao H, Brownell W. Chlorpromazine Alters Outer Hair Cell Electromotility. Otolaryngology 2001, 125: 71-76. PMID: 11458218, DOI: 10.1067/mhn.2001.116446.Peer-Reviewed Original ResearchConceptsOuter hair cellsHair cellsDose-dependent depolarizationGuinea pig outer hair cellsEffect of chlorpromazineElectromotile responseAntipsychotic medicationChlorpromazine treatmentHearing thresholdsLarge dosesCochlear sensitivityOtoacoustic emissionsInner earChlorpromazineOuter Hair Cell ElectromotilityHair cell electromotilityOHC electromotilityMembrane voltageRecording conditionsCellsMedicationsResponseElectromotility