2023
Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise
Liu L, Liang C, Chen J, Fang S, Zhao H. Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise. Science Advances 2023, 9: eadf4144. PMID: 36753545, PMCID: PMC9908021, DOI: 10.1126/sciadv.adf4144.Peer-Reviewed Original ResearchConceptsActive cochlear amplificationCochlear amplificationHeterozygous mutationsPermanent hearing threshold shiftHearing threshold shiftCochlear lateral wallNonsyndromic hearing lossHearing lossMouse modelGeneral populationNoise exposureThreshold shiftHeterozygote carriersHearing sensitivityLateral wallJunction genesGap junction genesPotential generationUnexpected findingExposureMutationsOversensitivityProtein prestinDeafness
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
Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communication
Zong L, Zhu Y, Liang R, Zhao H. Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communication. Scientific Reports 2016, 6: 19884. PMID: 26814383, PMCID: PMC4728487, DOI: 10.1038/srep19884.Peer-Reviewed Original ResearchConceptsGenetic communicationGap junction channelsGene regulationGene expressionIntercellular transferJunction channelsSmall regulatory RNAsNovel mechanismSpecific cell typesPassage of ionsRegulatory RNAsCellular processesOrgan developmentConnexin mutationsDifferent miRNAsRecipient cellsMiRNAsCell typesNeighboring cellsCell proliferationConnexin expressionImportant roleMiRNA levelsGap junctionsCell lines
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 causeMiceDeafnessDisorders
2013
Active cochlear amplification is dependent on supporting cell gap junctions
Zhu Y, Liang C, Chen J, Zong L, Chen G, Zhao H. Active cochlear amplification is dependent on supporting cell gap junctions. Nature Communications 2013, 4: 1786. PMID: 23653198, PMCID: PMC3675877, DOI: 10.1038/ncomms2806.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory ThresholdCochlear Microphonic PotentialsConnexin 26ConnexinsEvoked Potentials, Auditory, Brain StemGap JunctionsGene DeletionGene TargetingHair Cells, Auditory, OuterHearing LossLabyrinth Supporting CellsMiceMice, KnockoutMolecular Motor ProteinsNonlinear DynamicsOtoacoustic Emissions, SpontaneousSpiral GanglionConceptsActive cochlear amplificationOuter hair cellsCell gap junctionsHearing lossCochlear amplificationHair cellsGap junctionsDistortion product otoacoustic emissionsOuter hair cell electromotilityHair cell electromotilitySevere hearing lossProduct otoacoustic emissionsShorter outer hair cellsHair-bundle movementsOuter pillar cellsLeftward shiftOtoacoustic emissionsAcoustic stimulationDeiters' cellsHearing sensitivityConnexin 26Active cochlear mechanicsNovel findingsPillar cellsBundle movement
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 degeneration
2011
Pannexin channels are not gap junction hemichannels
Sosinsky G, Boassa D, Dermietzel R, Duffy H, Laird D, MacVicar B, Naus C, Penuela S, Scemes E, Spray D, Thompson R, Zhao H, Dahl G. Pannexin channels are not gap junction hemichannels. Channels 2011, 5: 193-197. PMID: 21532340, PMCID: PMC3704572, DOI: 10.4161/chan.5.3.15765.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 expressionCellular characterization of Connexin26 and Connnexin30 expression in the cochlear lateral wall
Liu Y, Zhao H. Cellular characterization of Connexin26 and Connnexin30 expression in the cochlear lateral wall. Cell And Tissue Research 2008, 333: 395. PMID: 18581144, PMCID: PMC2548271, DOI: 10.1007/s00441-008-0641-5.Peer-Reviewed Original ResearchHemichannel-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
Distinct and gradient distributions of connexin26 and connexin30 in the cochlear sensory epithelium of guinea pigs
Zhao H, Yu N. Distinct and gradient distributions of connexin26 and connexin30 in the cochlear sensory epithelium of guinea pigs. The Journal Of Comparative Neurology 2006, 499: 506-518. PMID: 16998915, PMCID: PMC2553046, DOI: 10.1002/cne.21113.Peer-Reviewed Original ResearchConceptsCochlear sensory epitheliumSensory epitheliumGuinea pigsHensen's cellsDeiters' cellsSpiral ganglion neuronsPillar cellsExpression of Cx26Auditory sensory epitheliumDistinct cellular expressionGanglion neuronsCochlear apexCx26 labelingCell bodiesCx26 expressionImmunofluorescent stainingEpitheliumHair cellsCellular expressionCx30Dense labelingClaudius cellsCell preparationsPredominant isoformCellular distributionGap 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
Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear
Zhao H, Yu N, Fleming C. Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 18724-18729. PMID: 16344488, PMCID: PMC1317927, DOI: 10.1073/pnas.0506481102.Peer-Reviewed Original ResearchConceptsHemichannel-mediated ATP releaseHair cellsGap junctional blockerActive cochlear amplifierAuditory sensory hair cellsSensory hair cellsEffect of ATPP2 receptorsExtracellular Ca2OHC electromotilityCochlear sensitivityATP releaseConnexin gap junctionsExtracellular ATPConnexin expressionInner earImmunofluorescent stainingHearing controlsHearing sensitivityOuter hair cell electromotilityCochleaHair cell electromotilityConnexin hemichannelsCochlear fluidsGap junctional channelsConnexin26 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