2023
The biology of hearing and hearing loss: New insights from naked mole-rats into mechanisms and adaptive responses
Pyott S, Jagersma J, van Tuinen M, Koch U, Lauer A, Park T, Lysakowski A, Santos-Sacchi J, Kumar S, Ryugo D. The biology of hearing and hearing loss: New insights from naked mole-rats into mechanisms and adaptive responses. The Journal Of The Acoustical Society Of America 2023, 154: a298-a299. DOI: 10.1121/10.0023589.Peer-Reviewed Original ResearchBiology of hearingBundle proteinHair bundle proteinAdaptive responseAmino acid substitutionsEusocial lifestyleEvolutionary legacySubterranean speciesPositive selectionComparative organizationAcid substitutionsHair bundlesCochlear amplificationBiologySpeciesProteinNew insightsHearing lossPoor hearingComparative approachDisease modelsMechanistic approachCentral auditory structuresCentral compensationRats resultsDifferential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding
Zhang Y, Lin G, Xue N, Wang Y, Du T, Liu H, Xiong W, Shang W, Wu H, Song L. Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding. The FASEB Journal 2023, 37: e23167. PMID: 37651093, DOI: 10.1096/fj.202300457rr.Peer-Reviewed Original ResearchConceptsAge-related hearing lossHigh-fat dietHearing lossEffects of HFDLoss of OHCsActivation of TRPV1Sensorineural hearing lossCBA/CaJPlace codingCochlear frequency selectivityTRPV1 expressionOHC functionInflammatory responseCommon causeHFD cohortGenetic backgroundYounger ageArachidonic acidCochlear lengthHair cellsPrestin levelsLipid homeostasisRescuing effectCochlear amplificationAgeMegahertz Sampling of Prestin (SLC26a5) Voltage-Sensor Charge Movements in Outer Hair Cell Membranes Reveals Ultrasonic Activity that May Support Electromotility and Cochlear Amplification
Santos-Sacchi J, Bai J, Navaratnam D. Megahertz Sampling of Prestin (SLC26a5) Voltage-Sensor Charge Movements in Outer Hair Cell Membranes Reveals Ultrasonic Activity that May Support Electromotility and Cochlear Amplification. Journal Of Neuroscience 2023, 43: 2460-2468. PMID: 36868859, PMCID: PMC10082455, DOI: 10.1523/jneurosci.2033-22.2023.Peer-Reviewed Original ResearchConceptsConformational switchingMammalian hearingMembrane motor proteinCochlear amplificationMotor protein prestinVoltage-sensor charge movementOuter hair cell electromotilityHair cell electromotilityProtein prestinMotor proteinsConformation switchingCharge movementPrestinPrestin activityCell membraneOHC electromotilityHair cell membraneElectromotilityTransmembrane voltageOrgan of CortiAmplificationMammalsMembrane capacitanceProteinCx26 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
2022
Physiology and biophysics of outer hair cells: The cells of Dallos
Santos-Sacchi J, Navaratnam D. Physiology and biophysics of outer hair cells: The cells of Dallos. Hearing Research 2022, 423: 108525. PMID: 35599199, DOI: 10.1016/j.heares.2022.108525.Peer-Reviewed Original ResearchConceptsOuter hair cellsHair cellsBasic physiologyCochlear amplificationHearing researchCellsPhysiologySingle particle cryo-EM structure of the outer hair cell motor protein prestin
Butan C, Song Q, Bai JP, Tan WJT, Navaratnam D, Santos-Sacchi J. Single particle cryo-EM structure of the outer hair cell motor protein prestin. Nature Communications 2022, 13: 290. PMID: 35022426, PMCID: PMC8755724, DOI: 10.1038/s41467-021-27915-z.Peer-Reviewed Original ResearchConceptsTransmembrane domainProtein prestinSingle-particle cryo-EM structuresAnti-sigma factor antagonist domainOuter hair cell motor protein prestinCryo-EM structureCryo-electron microscopyMotor protein prestinSLC26 family membersSulfate transportersTransmembrane segmentsPrestin functionÅ resolutionPrestinOHC electromotilityOpen stateCochlear amplificationPutative mechanismsFamily membersDomainRepeatsSLC26A9TransportersMutationsElectromotility
2021
Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells
Zhao H, Liu L, Yu N, Zhu Y, Mei L, Chen J, Liang C. Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells. Journal Of Neurophysiology 2021, 127: 313-327. PMID: 34907797, PMCID: PMC8759971, DOI: 10.1152/jn.00468.2021.Peer-Reviewed Original ResearchConceptsOuter hair cellsActive cochlear amplificationCochlear efferent systemDistortion product otoacoustic emissionsEfferent systemEfferent pathwaysHearing sensitivityMedial olivocochlear efferent fibersPresynaptic vesicular acetylcholine transportersGap junctionsOlivocochlear efferent fibersHair cellsApplication of acetylcholineCochlear supporting cellsProtection of hearingVesicular acetylcholine transporterActive cochlear amplifierCochlear amplificationPostsynaptic ACh receptorsProduct otoacoustic emissionsMOC efferent systemHair cell activityEfferent nervesEfferent inhibitionEfferent fibersState dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
Santos-Sacchi J, Navaratnam D, Tan WJT. State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance. Scientific Reports 2021, 11: 16149. PMID: 34373481, PMCID: PMC8352928, DOI: 10.1038/s41598-021-95121-4.Peer-Reviewed Original Research
2020
Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats
Pyott SJ, van Tuinen M, Screven LA, Schrode KM, Bai JP, Barone CM, Price SD, Lysakowski A, Sanderford M, Kumar S, Santos-Sacchi J, Lauer AM, Park TJ. Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats. Current Biology 2020, 30: 4329-4341.e4. PMID: 32888484, PMCID: PMC8109146, DOI: 10.1016/j.cub.2020.08.035.Peer-Reviewed Original ResearchConceptsHair bundle morphologyAmino acid substitutionsAltered hearingLink proteinAcid substitutionsUnique evolutionary trajectoryMolecular evolutionary analysisCochlear amplificationEvolutionary characterizationEvolutionary analysisHuman hearing lossEvolutionary trajectoriesBundle morphologyPrestin functionAfrican Mole-RatsCodon levelSelection pressureSubterranean lifestyleSubterranean rodentsMole-RatUnique lifestyleProteinHair cellsSpeciesOuter hair cellsComplex nonlinear capacitance in outer hair cell macro-patches: effects of membrane tension
Santos-Sacchi J, Tan W. Complex nonlinear capacitance in outer hair cell macro-patches: effects of membrane tension. Scientific Reports 2020, 10: 6222. PMID: 32277153, PMCID: PMC7148382, DOI: 10.1038/s41598-020-63201-6.Peer-Reviewed Original ResearchMaturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion
Zhai F, Song L, Bai JP, Dai C, Navaratnam D, Santos-Sacchi J. Maturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion. Neuroscience 2020, 431: 128-133. PMID: 32061780, PMCID: PMC8720582, DOI: 10.1016/j.neuroscience.2020.02.003.Peer-Reviewed Original ResearchConceptsMembrane motor proteinVoltage-dependent proteinsMembrane insertionOuter hair cellsMotor proteinsPrestin densityHEK cell linesConformational changesBiophysical forcesOHC electromotilityProteinCell linesMembrane potentialCooperative interactionsPrestinHair cellsCochlear amplificationTransmembrane voltageNonlinear capacitanceMammalsTraffickingVoltage-induced shiftElectromotilityMaturationMembrane
2019
Voltage Does Not Drive Prestin (SLC26a5) Electro-Mechanical Activity at High Frequencies Where Cochlear Amplification Is Best
Santos-Sacchi J, Tan W. Voltage Does Not Drive Prestin (SLC26a5) Electro-Mechanical Activity at High Frequencies Where Cochlear Amplification Is Best. IScience 2019, 22: 392-399. PMID: 31812809, PMCID: PMC6911985, DOI: 10.1016/j.isci.2019.11.036.Peer-Reviewed Original ResearchPrestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti
Bai JP, Navaratnam D, Santos-Sacchi J. Prestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti. Scientific Reports 2019, 9: 16460. PMID: 31712635, PMCID: PMC6848539, DOI: 10.1038/s41598-019-52965-1.Peer-Reviewed Original ResearchConceptsOuter hair cellsPostnatal dayVoltage-sensor charge movementAltricial animalsPostnatal developmentCochlear placeElectrical correlatesHair cellsMouse organsCochlear amplificationEarly developmentAuditory frequencyPrestin activityAuditory capabilitiesCellsCharge movementHigh frequencyResponse increasesPrestin functionMiceActivityMonthsCourse
2018
The Frequency Response of Outer Hair Cell Voltage-Dependent Motility Is Limited by Kinetics of Prestin
Santos-Sacchi J, Tan W. The Frequency Response of Outer Hair Cell Voltage-Dependent Motility Is Limited by Kinetics of Prestin. Journal Of Neuroscience 2018, 38: 5495-5506. PMID: 29899032, PMCID: PMC6001036, DOI: 10.1523/jneurosci.0425-18.2018.Peer-Reviewed Original ResearchConceptsFrequency responseVoltage excitationNonlinear capacitanceFlat frequency responseLow-pass behaviorInterrogation frequencyMechanical responsePiezoelectric couplingCutoff frequencyLow-pass characteristicsLow passElectrical signatureLimiting timeOrders of magnitudeAmplification gainCochlear amplificationKHzΜsMembrane protein prestinVoltageKineticsCapacitanceDamage resultsPhase correspondsElectricalKnockout 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
Progressive 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
Tyrosine motifs are required for prestin basolateral membrane targeting
Zhang Y, Moeini-Naghani I, Bai J, Santos-Sacchi J, Navaratnam DS. Tyrosine motifs are required for prestin basolateral membrane targeting. Biology Open 2015, 4: 197-205. PMID: 25596279, PMCID: PMC4365488, DOI: 10.1242/bio.201410629.Peer-Reviewed Original ResearchBasolateral targetingBasolateral surfaceOuter hair cellsBasolateral plasma membraneEpithelial sortingHair cellsYXXΦ motifTyrosine motifEarly endosomesPlasma membranePolarized epitheliumTyrosine residuesPrestinGolgiMDCK cellsTyrosine side chainAP1BPhenotypic measuresBasolateral membraneModel systemEpithelial cellsCochlear amplificationMotifMutationsResidues
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 deficiencyCochleaInterventionChloride-driven Electromechanical Phase Lags at Acoustic Frequencies Are Generated by SLC26a5, the Outer Hair Cell Motor Protein
Santos-Sacchi J, Song L. Chloride-driven Electromechanical Phase Lags at Acoustic Frequencies Are Generated by SLC26a5, the Outer Hair Cell Motor Protein. Biophysical Journal 2014, 107: 126-133. PMID: 24988347, PMCID: PMC4119270, DOI: 10.1016/j.bpj.2014.05.018.Peer-Reviewed Original Research
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