2022
Outer hair cell function is normal in βV spectrin knockout mice
Stankewich MC, Bai JP, Stabach PR, Khan S, Tan WJT, Surguchev A, Song L, Morrow JS, Santos-Sacchi J, Navaratnam DS. Outer hair cell function is normal in βV spectrin knockout mice. Hearing Research 2022, 423: 108564. PMID: 35864018, DOI: 10.1016/j.heares.2022.108564.Peer-Reviewed Original ResearchConceptsOuter hair cellsAuditory brainstem response wavesAuditory thresholdOuter hair cell functionSpiral ganglion neuronsEfferent nerve fibersHair cell functionNumber of afferentsGanglion neuronsNerve fibersKnockout miceNeuronal structuresMiceHair cellsCell functionElectromechanical activityPutative roleType IOngoing investigationExon deletionsSynaptopathyAfferentsData supportResponse wavesNeuronsPhysiology 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 Research
2021
Genes related to SNPs identified by Genome-wide association studies of age-related hearing loss show restriction to specific cell types in the adult mouse cochlea
Xue N, Song L, Song Q, Santos-Sacchi J, Wu H, Navaratnam D. Genes related to SNPs identified by Genome-wide association studies of age-related hearing loss show restriction to specific cell types in the adult mouse cochlea. Hearing Research 2021, 410: 108347. PMID: 34536825, DOI: 10.1016/j.heares.2021.108347.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingApical cell polarityGenome-wide association studiesAdult mouse cochleaSpecific cell typesCell polaritySubtypes of cellsSignificant genetic componentSingle nucleotide polymorphismsVesicle recyclingRNA sequencingAssociation studiesGenesVarying ExpressionCell typesGenetic componentNucleotide polymorphismsSNPsMouse cochleaCell functionGenesetsHair cellsHair cell functionSignificant overlapExpressionEfferent feedback controls bilateral auditory spontaneous activity
Wang Y, Sanghvi M, Gribizis A, Zhang Y, Song L, Morley B, Barson DG, Santos-Sacchi J, Navaratnam D, Crair M. Efferent feedback controls bilateral auditory spontaneous activity. Nature Communications 2021, 12: 2449. PMID: 33907194, PMCID: PMC8079389, DOI: 10.1038/s41467-021-22796-8.Peer-Reviewed Original ResearchConceptsSpontaneous activityEfferent modulationEfferent pathwaysMedial olivocochlear systemCentral nervous systemCentral auditory systemInner hair cellsAuditory systemNicotinic acetylcholine receptorsSpontaneous activity patternsOlivocochlear systemHearing onsetEfferent systemChemogenetic experimentsBilateral couplingNervous systemAcetylcholine receptorsCircuit formationEfferent feedbackFiring patternsHair cellsΑ9/Auditory sensitivityBilateral correlationActivity patterns
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 cellsCalcium‐induced calcium release in proximity to hair cell BK channels revealed by PKA activation
Bai J, Xue N, Lawal O, Nyati A, Santos‐Sacchi J, Navaratnam D. Calcium‐induced calcium release in proximity to hair cell BK channels revealed by PKA activation. Physiological Reports 2020, 8: e14449. PMID: 32748549, PMCID: PMC7399380, DOI: 10.14814/phy2.14449.Peer-Reviewed Original ResearchConceptsBK channelsBK currentsCalcium-activated potassium channelsLarge-conductance calcium-activated potassium channelsCalcium-induced calcium releaseEntry of CaSlo subunitSynaptic releaseCalcium releaseChicken hair cellsPotassium channelsHair cellsIP3 receptorCICRA ActivationPKA activationActivationCritical roleImagingReleaseRyanodineMaturation 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
2017
Prestin: Molecular Mechanisms Underlying Outer Hair Cell Electromotility
Santos-Sacchi J, Navaratnam D, Raphael R, Oliver D. Prestin: Molecular Mechanisms Underlying Outer Hair Cell Electromotility. Springer Handbook Of Auditory Research 2017, 62: 113-145. DOI: 10.1007/978-3-319-52073-5_5.Peer-Reviewed Original ResearchOuter hair cellsMammalian inner earOuter Hair Cell ElectromotilityHair cell electromotilitySLC26 familyMolecular mechanismsMembrane lipidsConformational changesMechanical feedback mechanismMolecular motorsTension sensitivityPrestinHair cellsVoltage-sensor charge movementAnion transportersReceptor potentialProteinMolecular conformational changesInner earStructural determinationIntracellular chlorideCharge movementTraffickingFeedback mechanismMechanismCurrent carried by the Slc26 family member prestin does not flow through the transporter pathway
Bai JP, Moeini-Naghani I, Zhong S, Li FY, Bian S, Sigworth FJ, Santos-Sacchi J, Navaratnam D. Current carried by the Slc26 family member prestin does not flow through the transporter pathway. Scientific Reports 2017, 7: 46619. PMID: 28422190, PMCID: PMC5395958, DOI: 10.1038/srep46619.Peer-Reviewed Original Research
2016
Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels
Lv C, Stewart WJ, Akanyeti O, Frederick C, Zhu J, Santos-Sacchi J, Sheets L, Liao JC, Zenisek D. Synaptic Ribbons Require Ribeye for Electron Density, Proper Synaptic Localization, and Recruitment of Calcium Channels. Cell Reports 2016, 15: 2784-2795. PMID: 27292637, PMCID: PMC5334794, DOI: 10.1016/j.celrep.2016.05.045.Peer-Reviewed Original ResearchConceptsNeuromast hair cellsProper synaptic localizationHair cellsSynaptic ribbonsZebrafish genesProper localizationCalcium channelsSynaptic vesiclesSmall vesiclesEnhanced exocytosisFrameshift mutationRibeye proteinsSynaptic localizationVesiclesRelease sitesCellsRibeyeRibbon-like structuresNon-spiking cellsSensory systemsLocalizationGenesExocytosisSimilar numberProtein
2015
Auditory Pathology in a Transgenic mtTFB1 Mouse Model of Mitochondrial Deafness
McKay SE, Yan W, Nouws J, Thormann MJ, Raimundo N, Khan A, Santos-Sacchi J, Song L, Shadel GS. Auditory Pathology in a Transgenic mtTFB1 Mouse Model of Mitochondrial Deafness. American Journal Of Pathology 2015, 185: 3132-3140. PMID: 26552864, PMCID: PMC5801480, DOI: 10.1016/j.ajpath.2015.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsApoptosisDeafnessDisease Models, AnimalDNA, MitochondrialEvoked Potentials, Auditory, Brain StemHair Cells, Auditory, InnerMice, Inbred C57BLMice, KnockoutMice, TransgenicMitochondrial DiseasesMutationOrgan of CortiReaction TimeSignal TransductionSpiral GanglionStria VascularisTranscription FactorsConceptsAMP kinaseReactive oxygen species-mediated activationTranscription factor E2F1A1555G mutationAuditory pathologyHair cellsTFB1MHearing loss phenotypeRRNA geneAMPK-α1AMPK activityProlonged wave I latencyLoss phenotypeMitochondrial pathologyNonsyndromic deafnessTransgenic mouse strainWave I latencySpiral ganglion neuronsProgressive hearing lossMitochondrial deafnessPotential therapeutic valueDNA causeG mutationOuter hair cellsI latencyTyrosine 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
Charaterization of Calcium Current and Exocytosis in Zebrafish Lateral Line Hair Cells During Development
Lv C, Santos-Sacchi J, Zenisek D. Charaterization of Calcium Current and Exocytosis in Zebrafish Lateral Line Hair Cells During Development. Biophysical Journal 2014, 106: 597a. DOI: 10.1016/j.bpj.2013.11.3305.Peer-Reviewed Original Research
2013
Patch-Clamp Recordings from Lateral Line Neuromast Hair Cells of the Living Zebrafish
Ricci AJ, Bai JP, Song L, Lv C, Zenisek D, Santos-Sacchi J. Patch-Clamp Recordings from Lateral Line Neuromast Hair Cells of the Living Zebrafish. Journal Of Neuroscience 2013, 33: 3131-3134. PMID: 23407967, PMCID: PMC3684625, DOI: 10.1523/jneurosci.4265-12.2013.Peer-Reviewed Original ResearchConceptsHair cellsSynaptic vesicle releaseNeuromast hair cellsLiving zebrafishBiological discoveryIonic channel activityZebrafishVesicle releaseChannel activityPhysiological activityLateral lineJunctional couplingCellsDetailed understandingPatch-clamp recordingsVestibular peripheryFishNeuromastsActivityDiscoveryFirst recordingChapter 25 Audition
Brown M, Santos-Sacchi J. Chapter 25 Audition. 2013, 553-576. DOI: 10.1016/b978-0-12-385870-2.00025-1.Peer-Reviewed Original ResearchHair cellsOuter hair cellsMore apical locationsCochlear nucleusMedial geniculateNerve fibersAuditory brainstemAuditory cortexInferior colliculusAuditory nerveSuperior oliveComplex sound stimuliSensitivity of hearingCochlear implantsInteraural level differencesInner earCentral pathwaysReceptor cellsSound stimuliAuditory systemInteraural timeSound localizationIon channelsApical locationMechanoreceptors
2011
Chloride Dependent Coupling of Molecular to Cellular Mechanics in the Outer Hair Cell of Corti's Organ
Song L, Santos-Sacchi J, Shera C, Olson E. Chloride Dependent Coupling of Molecular to Cellular Mechanics in the Outer Hair Cell of Corti's Organ. AIP Conference Proceedings 2011, 1403: 179-184. DOI: 10.1063/1.3658083.Peer-Reviewed Original ResearchCellular mechanicsConformational changesMotor protein prestinProtein prestinMolecular eventsLateral membranesOHC lateral membraneCellular expressionWhole cellsElectromotilityOuter Hair CellsPrestinHair cellsReceptor potentialNonlinear capacitanceMolecular conformational changesIntracellular chloride levelsCellsTight couplingOrgansOHC receptor potentialsExpressionMembraneNormal levelsVivoThe still magnificent outer hair cell
Santos-Sacchi J. The still magnificent outer hair cell. Otology Japan 2011, 17: 2-7. DOI: 10.11289/otoljpn1991.17.2.Peer-Reviewed Original ResearchThe magnificent outer hair cell of Corti's organ
Santos-Sacchi J. The magnificent outer hair cell of Corti's organ. Otology Japan 2011, 9: 111-115. DOI: 10.11289/otoljpn1991.9.111.Peer-Reviewed Original Research