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 wavesNeurons
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 patternsComprehensive somatosensory and neurological phenotyping of NCS1 knockout mice
Nguyen LD, Nolte LG, Tan WJT, Giuvelis D, Santos-Sacchi J, Bilsky E, Ehrlich BE. Comprehensive somatosensory and neurological phenotyping of NCS1 knockout mice. Scientific Reports 2021, 11: 2372. PMID: 33504822, PMCID: PMC7840744, DOI: 10.1038/s41598-021-81650-5.Peer-Reviewed Original ResearchConceptsNeuronal calcium sensor-1Peripheral nervous systemNervous systemMale miceKnockout micePaclitaxel-induced peripheral neuropathyKO modelKO male miceNCS1 expressionMammalian nervous systemPrecise physiological significanceSex-specific effectsPeripheral neuropathyFemale miceModulatory roleBehavioral testsPharmacological targetsMiceNeurodegenerative diseasesClinical interestMemory acquisitionMotor performancePathological statesAffective behaviorDisease
2019
Prestin 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 functionMiceActivityMonthsCourseOuter hair cell electromotility is low-pass filtered relative to the molecular conformational changes that produce nonlinear capacitance
Santos-Sacchi J, Iwasa KH, Tan W. Outer hair cell electromotility is low-pass filtered relative to the molecular conformational changes that produce nonlinear capacitance. The Journal Of General Physiology 2019, 151: 1369-1385. PMID: 31676485, PMCID: PMC6888751, DOI: 10.1085/jgp.201812280.Peer-Reviewed Original ResearchModulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice
El-Hassar L, Song L, Tan WJT, Large CH, Alvaro G, Santos-Sacchi J, Kaczmarek LK. Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice. Journal Of Neuroscience 2019, 39: 4797-4813. PMID: 30936239, PMCID: PMC6561694, DOI: 10.1523/jneurosci.0839-18.2019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysAuditory PerceptionBrain StemCochlear NucleusElectrophysiological PhenomenaEvoked Potentials, Auditory, Brain StemFemaleFragile X Mental Retardation ProteinFragile X SyndromeHydantoinsIn Vitro TechniquesMaleMiceMice, KnockoutPatch-Clamp TechniquesPyridinesShaw Potassium ChannelsConceptsAuditory brainstem responseWild-type animalsRepetitive firingABR wave ICurrent-clamp recordingsAuditory brainstem nucleiVoltage-clamp recordingsHigh-frequency firingSingle action potentialFragile X syndromeTrapezoid bodyBrainstem nucleiBrainstem responseMedial nucleusAuditory brainstemAuditory nerveWave IWave IVAction potentialsSensory stimuliKv3.1 channelsCentral processingMental retardation proteinHigh sound levelsMice
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 correspondsElectrical
2017
Novel Role of the Mitochondrial Protein Fus1 in Protection from Premature Hearing Loss via Regulation of Oxidative Stress and Nutrient and Energy Sensing Pathways in the Inner Ear
Tan WJ, Song L, Graham M, Schettino A, Navaratnam D, Yarbrough WG, Santos-Sacchi J, Ivanova AV. Novel Role of the Mitochondrial Protein Fus1 in Protection from Premature Hearing Loss via Regulation of Oxidative Stress and Nutrient and Energy Sensing Pathways in the Inner Ear. Antioxidants & Redox Signaling 2017, 27: 489-509. PMID: 28135838, PMCID: PMC5564041, DOI: 10.1089/ars.2016.6851.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsAntioxidantsDisease Models, AnimalEar, InnerEvoked Potentials, Auditory, Brain StemGene Knockout TechniquesHearing LossHumansMiceMicroscopy, Electron, TransmissionMitochondriaOxidative StressProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseSignal TransductionSpiral GanglionTOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsAge-related hearing lossAuditory brainstem responseHearing lossKO miceEndocochlear potentialOxidative stressMitochondrial dysfunctionMitochondrial dysfunction/oxidative stressEnergy sensing pathwaysNovel therapeutic strategiesMolecular mechanismsPremature hearing lossCochlear stria vascularisMajor hearing lossChronic mitochondrial dysfunctionMetabolic etiologyWorldwide epidemicBrainstem responseClinical trialsVascular pathologyTherapeutic strategiesPathological alterationsABR parametersAO treatmentStria vascularis
2012
Mitochondrial Stress Engages E2F1 Apoptotic Signaling to Cause Deafness
Raimundo N, Song L, Shutt TE, McKay SE, Cotney J, Guan MX, Gilliland TC, Hohuan D, Santos-Sacchi J, Shadel GS. Mitochondrial Stress Engages E2F1 Apoptotic Signaling to Cause Deafness. Cell 2012, 148: 716-726. PMID: 22341444, PMCID: PMC3285425, DOI: 10.1016/j.cell.2011.12.027.Peer-Reviewed Original ResearchConceptsAltered reactive oxygen speciesReactive oxygen speciesMitochondrial ribosome functionMitochondrial disease modelTranscription factor E2F1Tissue-specific pathologyROS-dependent activationRibosome functionRRNA methylationMitochondrial stressApoptotic signalingTissue specificityMtDNA mutationsMetabolic signalingAMP kinaseMultiple tissuesMitochondrial dysfunctionOxygen speciesE2F1MethylationSignalingG cellsEnvironmental factorsApoptosisMice exhibit
2010
Effect of capsaicin on potassium conductance and electromotility of the guinea pig outer hair cell
Wu T, Song L, Shi X, Jiang Z, Santos-Sacchi J, Nuttall A. Effect of capsaicin on potassium conductance and electromotility of the guinea pig outer hair cell. Hearing Research 2010, 272: 117-124. PMID: 21044673, PMCID: PMC3387680, DOI: 10.1016/j.heares.2010.10.010.Peer-Reviewed Original ResearchConceptsOuter hair cellsTRPV-1 channelsHair cellsPrimary sensory neuronsEffects of capsaicinGuinea pig outer hair cellsSensory neuronsPharmacological actionsCapsaicinPotassium conductancePotent blockerPharmacological propertiesDirect actionNovel actionCochlear amplificationK conductanceAuditory effectsClassic activatorAuditory receptionCellsNociceptionElectromotilityBlockersNew findingsNeuronsA highly expressing Tet-inducible cell line recapitulates in situ developmental changes in prestin's Boltzmann characteristics and reveals early maturational events
Bian S, Koo BW, Kelleher S, Santos-Sacchi J, Navaratnam DS. A highly expressing Tet-inducible cell line recapitulates in situ developmental changes in prestin's Boltzmann characteristics and reveals early maturational events. American Journal Of Physiology - Cell Physiology 2010, 299: c828-c835. PMID: 20631244, PMCID: PMC3774197, DOI: 10.1152/ajpcell.00182.2010.Peer-Reviewed Original Research
2009
Prestin's Anion Transport and Voltage-Sensing Capabilities Are Independent
Bai JP, Surguchev A, Montoya S, Aronson PS, Santos-Sacchi J, Navaratnam D. Prestin's Anion Transport and Voltage-Sensing Capabilities Are Independent. Biophysical Journal 2009, 96: 3179-3186. PMID: 19383462, PMCID: PMC2718310, DOI: 10.1016/j.bpj.2008.12.3948.Peer-Reviewed Original ResearchMeSH Keywords4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAnalysis of VarianceAnimalsAnion Transport ProteinsAntiportersCarbon RadioisotopesChloridesCHO CellsCricetinaeCricetulusElectric CapacitanceFormatesGerbillinaeIon TransportMiceMutation, MissenseOxalatesPatch-Clamp TechniquesSalicylatesSulfate TransportersConceptsClosest phylogenetic relativesTransmembrane regionSLC26 anion transporter familyMammalian outer hair cellsMembrane protein prestinPrestin's motor functionAnion transportPhylogenetic relativesAnion transporter familyTransporter familyProtein prestinChloride-binding siteGating charge movementPrestinCharge movementHair cellsOuter hair cellsResiduesMechanistic conceptsVoltage sensingTransport capabilityCellsVoltage sensorPrevious observationsUptake studies
2008
Cochlear Mechanics: No Shout but a Twist in the Absence of Prestin
Santos-Sacchi J. Cochlear Mechanics: No Shout but a Twist in the Absence of Prestin. Current Biology 2008, 18: r304-r306. PMID: 18397741, DOI: 10.1016/j.cub.2008.02.019.Peer-Reviewed Original Research
2007
Developmental Expression of the Outer Hair Cell Motor Prestin in the Mouse
Abe T, Kakehata S, Kitani R, Maruya S, Navaratnam D, Santos-Sacchi J, Shinkawa H. Developmental Expression of the Outer Hair Cell Motor Prestin in the Mouse. The Journal Of Membrane Biology 2007, 215: 49-56. PMID: 17415610, PMCID: PMC4154540, DOI: 10.1007/s00232-007-9004-5.Peer-Reviewed Original ResearchConceptsLateral membranesOuter hair cellsMouse outer hair cellsMotor protein activitySteady-state levelsKnockout experimentsProtein activityDevelopmental expressionMembrane tensionGenetic modificationConformational fluctuationsCellular mechanismsMotor moleculesMolecular motorsOnset of hearingMorphological estimatesProtein densityEarly maturationQuantitative polymerase chain reactionHair cellsVpkCmDevelopmental dataCochlear amplificationMaturationFull maturation
2005
Glibenclamide Stimulates Fluid Secretion in Rodent Cholangiocytes Through a Cystic Fibrosis Transmembrane Conductance Regulator-Independent Mechanism
Spirlì C, Fiorotto R, Song L, Santos-Sacchi J, Okolicsanyi L, Masier S, Rocchi L, Vairetti MP, de Bernard M, Melero S, Pozzan T, Strazzabosco M. Glibenclamide Stimulates Fluid Secretion in Rodent Cholangiocytes Through a Cystic Fibrosis Transmembrane Conductance Regulator-Independent Mechanism. Gastroenterology 2005, 129: 220-233. PMID: 16012949, DOI: 10.1053/j.gastro.2005.03.048.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP-Binding Cassette TransportersBile DuctsBody FluidsCalciumCell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorElectric CapacitanceElectric ConductivityGlyburideHypoglycemic AgentsLiverMiceMice, Inbred CFTRPatch-Clamp TechniquesPotassium ChannelsPotassium Channels, Inwardly RectifyingRatsReceptors, DrugSulfonylurea ReceptorsConceptsCystic fibrosisBiliary ductsCholangiocyte secretionFluid secretionAbility of glibenclamideCystic fibrosis transmembrane conductance regulatorIntracellular Ca 2Liver impairmentSevere complicationsLiver diseaseCholestatic diseaseRodent cholangiocytesGlibenclamideInhibitors of exocytosisAbstractTextFibrosisSecretionSecretory mechanismDiseaseMiceCholangiocytesRat cholangiocytesCFTR inhibitor
1993
Mapping the distribution of the outer hair cell motility voltage sensor by electrical amputation
Huang G, Santos-Sacchi J. Mapping the distribution of the outer hair cell motility voltage sensor by electrical amputation. Biophysical Journal 1993, 65: 2228-2236. PMID: 8298046, PMCID: PMC1225954, DOI: 10.1016/s0006-3495(93)81248-7.Peer-Reviewed Original Research
1985
A Ferritin-containing Cell Type in the Stria Vascularis of the Mouse Inner Ear
Santos-Sacchi J, Marovitz W. A Ferritin-containing Cell Type in the Stria Vascularis of the Mouse Inner Ear. Acta Oto-Laryngologica 1985, 100: 26-32. PMID: 4024891, DOI: 10.3109/00016488509108583.Peer-Reviewed Original Research
1982
An electronmicroscopic study of microtubules in the development of marginal cells of the mouse stria vascularis
Santos-Sacchi J. An electronmicroscopic study of microtubules in the development of marginal cells of the mouse stria vascularis. Hearing Research 1982, 6: 7-13. PMID: 7054137, DOI: 10.1016/0378-5955(82)90003-x.Peer-Reviewed Original ResearchConceptsMouse stria vascularisPlasma membraneCellular extensionsNumerous cellular processesMarginal cellsSheet-like extensionsCellular processesCell peripheryLength of microtubulesGolgi bodiesDepolymerization of microtubulesCytoplasmic microtubulesMicrotubulesNumerous microtubulesCell processesOrganellesMitochondriaStria vascularisCellsMembraneAdult miceCytoplasmVesiclesPlasmalemmaMicrotubles
1980
An Evaluation of Normal Strial Capillary Transport Using the Electron-Opaque Tracers Ferritin and Iron Dextran
Santos-Sacchi J, Marovitz W. An Evaluation of Normal Strial Capillary Transport Using the Electron-Opaque Tracers Ferritin and Iron Dextran. Acta Oto-Laryngologica 1980, 89: 12-26. PMID: 7405570, DOI: 10.3109/00016488009127103.Peer-Reviewed Original Research