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
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 cellsMaturation 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
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
2013
Chapter 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
Extracellular chloride regulation of Kv2.1, contributor to the major outward Kv current in mammalian outer hair cells
Li X, Surguchev A, Bian S, Navaratnam D, Santos-Sacchi J. Extracellular chloride regulation of Kv2.1, contributor to the major outward Kv current in mammalian outer hair cells. American Journal Of Physiology - Cell Physiology 2011, 302: c296-c306. PMID: 21940671, PMCID: PMC4054960, DOI: 10.1152/ajpcell.00177.2011.Peer-Reviewed Original ResearchThe 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
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 findingsNeurons
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
Anion Control of Voltage Sensing by the Motor Protein Prestin in Outer Hair Cells
Rybalchenko V, Santos-Sacchi J. Anion Control of Voltage Sensing by the Motor Protein Prestin in Outer Hair Cells. Biophysical Journal 2008, 95: 4439-4447. PMID: 18658219, PMCID: PMC2567960, DOI: 10.1529/biophysj.108.134197.Peer-Reviewed Original ResearchConceptsOuter hair cellsHair cellsCochlear amplificationSLC26 anion transporter familyMotor protein prestinMammalian cochlear amplificationVoltage-sensor charge movementAuditory responsivenessCorti's organAnion transporter familyTransporter familyProtein prestinMolecular motorsCharge movementPrestinOrgansCellsComplicated roleVoltage sensingCochlear 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
2004
On Membrane Motor Activity and Chloride Flux in the Outer Hair Cell: Lessons Learned from the Environmental Toxin Tributyltin
Song L, Seeger A, Santos-Sacchi J. On Membrane Motor Activity and Chloride Flux in the Outer Hair Cell: Lessons Learned from the Environmental Toxin Tributyltin. Biophysical Journal 2004, 88: 2350-2362. PMID: 15596517, PMCID: PMC1305283, DOI: 10.1529/biophysj.104.053579.Peer-Reviewed Original ResearchConceptsLateral membranesCell’s mechanical activityOuter hair cellsMammalian cochlear amplifierHair cellsMembrane motorMarine mammalsIntact outer hair cellsPotent abilityFood chainNonselective conductanceCl(-) homeostasisPrestinNanomolar concentrationsExtracellular Cl- concentrationCl fluxMembraneCellsNew environmental threatsMammalsChloride effectTributyltinEnvironmental threatsHomeostasisNonlinear capacitance