2023
Megahertz 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 ResearchMeSH KeywordsAnimalsCell MembraneCochleaGuinea PigsHair Cells, Auditory, OuterHearingMammalsUltrasonicsConceptsConformational 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 capacitanceProtein
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 ResearchMeSH KeywordsAnimalsCochleaEvoked Potentials, Auditory, Brain StemHair Cells, Auditory, OuterMiceMice, KnockoutOtoacoustic Emissions, SpontaneousSpectrinConceptsOuter 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 wavesNeuronsOn the frequency response of prestin charge movement in membrane patches
Santos-Sacchi J, Tan W. On the frequency response of prestin charge movement in membrane patches. Biophysical Journal 2022, 121: 2371-2379. PMID: 35598044, PMCID: PMC9279172, DOI: 10.1016/j.bpj.2022.05.020.Peer-Reviewed Original ResearchCell MembraneElectric CapacitanceHair Cells, Auditory, OuterMembrane PotentialsPatch-Clamp TechniquesProteinsPhysiology 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 ResearchSingle 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
Coupling between outer hair cell electromotility and prestin sensor charge depends on voltage operating point
Santos-Sacchi J, Tan WJT. Coupling between outer hair cell electromotility and prestin sensor charge depends on voltage operating point. Hearing Research 2021, 423: 108373. PMID: 34776274, PMCID: PMC9054947, DOI: 10.1016/j.heares.2021.108373.Peer-Reviewed Original ResearchMeSH KeywordsCochleaElectric CapacitanceHair Cells, Auditory, OuterHair Cells, VestibularPatch-Clamp TechniquesConceptsOperating voltage rangeFrequency responseAC voltage excitationSlow frequency responseVoltage operating pointNonlinear capacitanceOperating voltageOperating pointVoltage excitationVoltage rangeSpecial Issue Outer hair cellJoseph Santos-SacchiVoltageKumar NavaratnamLoadVoltage-sensor charge movementState 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
Complex 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 ResearchMeSH KeywordsAnimalsCells, CulturedElectric CapacitanceGuinea PigsHair Cells, Auditory, OuterMembrane PotentialsPatch-Clamp TechniquesPrimary Cell CultureProteinsSalicylatesMaturation 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 ResearchMeSH KeywordsAnimalsAnion Transport ProteinsCell MembraneElectric CapacitanceHair Cells, Auditory, OuterMembrane PotentialsPatch-Clamp TechniquesProteinsConceptsMembrane motor proteinVoltage-dependent proteinsMembrane insertionOuter hair cellsMotor proteinsPrestin densityHEK cell linesConformational changesBiophysical forcesOHC electromotilityProteinCell linesMembrane potentialCooperative interactionsPrestinHair cellsCochlear amplificationTransmembrane voltageNonlinear capacitanceMammalsTraffickingVoltage-induced shiftElectromotilityMaturationMembrane
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 ResearchThe speed limit of outer hair cell electromechanical activity
Santos-Sacchi J. The speed limit of outer hair cell electromechanical activity. HNO 2019, 67: 159-164. PMID: 30747242, DOI: 10.1007/s00106-019-0615-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PerceptionCochleaHair Cells, Auditory, OuterMembrane PotentialsOrgan of Corti
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 ResearchMeSH KeywordsAnimalsAuditory PerceptionFemaleGuinea PigsHair Cells, Auditory, OuterKineticsMaleMechanotransduction, CellularMiceMolecular Motor ProteinsProteinsConceptsFrequency responseVoltage excitationNonlinear capacitanceFlat frequency responseLow-pass behaviorInterrogation frequencyMechanical responsePiezoelectric couplingCutoff frequencyLow-pass characteristicsLow passElectrical signatureLimiting timeOrders of magnitudeAmplification gainCochlear amplificationKHzΜsMembrane protein prestinVoltageKineticsCapacitanceDamage resultsPhase correspondsElectrical
2016
A Walkthrough of Nonlinear Capacitance Measurement of Outer Hair Cells
Song L, Santos-Sacchi J. A Walkthrough of Nonlinear Capacitance Measurement of Outer Hair Cells. Methods In Molecular Biology 2016, 1427: 501-512. PMID: 27259945, DOI: 10.1007/978-1-4939-3615-1_28.Peer-Reviewed Original ResearchChloride Anions Regulate Kinetics but Not Voltage-Sensor Q max of the Solute Carrier SLC26a5
Santos-Sacchi J, Song L. Chloride Anions Regulate Kinetics but Not Voltage-Sensor Q max of the Solute Carrier SLC26a5. Biophysical Journal 2016, 110: 2551-2561. PMID: 27276272, PMCID: PMC4906268, DOI: 10.1016/j.bpj.2016.05.002.Peer-Reviewed Original Research
2015
An Electrical Inspection of the Subsurface Cisternae of the Outer Hair Cell
Song L, Santos-Sacchi J. An Electrical Inspection of the Subsurface Cisternae of the Outer Hair Cell. Biophysical Journal 2015, 108: 568-577. PMID: 25650924, PMCID: PMC4317539, DOI: 10.1016/j.bpj.2014.12.010.Peer-Reviewed Original Research
2014
Chloride-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 ResearchMeSH KeywordsAnimalsCell MovementChloridesGuinea PigsHair Cells, Auditory, OuterMembrane PotentialsProtein BindingProtein Structure, TertiaryProteinsReaction TimeSoundChloride and Salicylate Influence Prestin-dependent Specific Membrane Capacitance SUPPORT FOR THE AREA MOTOR MODEL* * This work was supported, in whole or in part, by National Institutes of Health Grant NIDCD DC00273 (to J. S. S.).
Santos-Sacchi J, Song L. Chloride and Salicylate Influence Prestin-dependent Specific Membrane Capacitance SUPPORT FOR THE AREA MOTOR MODEL* * This work was supported, in whole or in part, by National Institutes of Health Grant NIDCD DC00273 (to J. S. S.). Journal Of Biological Chemistry 2014, 289: 10823-10830. PMID: 24554714, PMCID: PMC4036195, DOI: 10.1074/jbc.m114.549329.Peer-Reviewed Original Research
2013
Disparities in voltage-sensor charge and electromotility imply slow chloride-driven state transitions in the solute carrier SLC26a5
Song L, Santos-Sacchi J. Disparities in voltage-sensor charge and electromotility imply slow chloride-driven state transitions in the solute carrier SLC26a5. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3883-3888. PMID: 23431177, PMCID: PMC3593883, DOI: 10.1073/pnas.1218341110.Peer-Reviewed Original Research
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 Research