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
On 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 Research
2020
Maturation 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
Outer 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 Research
2014
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.).
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
Real Time Measures of Prestin Charge and Fluorescence during Plasma Membrane Trafficking Reveal Sub-Tetrameric Activity
Bian S, Navaratnam D, Santos-Sacchi J. Real Time Measures of Prestin Charge and Fluorescence during Plasma Membrane Trafficking Reveal Sub-Tetrameric Activity. PLOS ONE 2013, 8: e66078. PMID: 23762468, PMCID: PMC3677934, DOI: 10.1371/journal.pone.0066078.Peer-Reviewed Original ResearchConceptsObligate tetramerPlasma membraneMembrane motor proteinIntegral membrane proteinsTetracycline-inducible cell lineMembrane proteinsMotor proteinsPrestin densityTemperature blockPrestinFluorescence measuresMembrane fluorescenceCell linesNonlinear capacitanceCochlear amplificationProteinTetramerMembraneFluorescencePrevious observationsVoltage clampFluorescence methodCellsAmplification
2010
A 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 ResearchConformational State-Dependent Anion Binding in Prestin: Evidence for Allosteric Modulation
Song L, Santos-Sacchi J. Conformational State-Dependent Anion Binding in Prestin: Evidence for Allosteric Modulation. Biophysical Journal 2010, 98: 371-376. PMID: 20141749, PMCID: PMC2814207, DOI: 10.1016/j.bpj.2009.10.027.Peer-Reviewed Original ResearchAllosteric RegulationAnimalsAnionsCell MembraneCells, CulturedCentral Nervous System AgentsChloridesElectric CapacitanceGuinea PigsHair Cells, Auditory, OuterInhibitory Concentration 50Membrane PotentialsModels, NeurologicalNonlinear DynamicsPatch-Clamp TechniquesProtein ConformationProteinsSalicylatesTemperature
2009
Fast Electromechanical Amplification in the Lateral Membrane of the Outer Hair Cell
Santos-Sacchi J, Navarrete E, Song L. Fast Electromechanical Amplification in the Lateral Membrane of the Outer Hair Cell. Biophysical Journal 2009, 96: 739-747. PMID: 19167318, PMCID: PMC2716482, DOI: 10.1016/j.bpj.2008.10.015.Peer-Reviewed Original Research
2006
Tuning in to the Amazing Outer Hair Cell: Membrane Wizardry with a Twist and Shout
He D, Zheng J, Kalinec F, Kakehata S, Santos-Sacchi J. Tuning in to the Amazing Outer Hair Cell: Membrane Wizardry with a Twist and Shout. The Journal Of Membrane Biology 2006, 209: 119-134. PMID: 16773497, DOI: 10.1007/s00232-005-0833-9.Peer-Reviewed Original Research
2005
On the Effect of Prestin on the Electrical Breakdown of Cell Membranes
Navarrete EG, Santos-Sacchi J. On the Effect of Prestin on the Electrical Breakdown of Cell Membranes. Biophysical Journal 2005, 90: 967-974. PMID: 16299081, PMCID: PMC1367121, DOI: 10.1529/biophysj.105.064105.Peer-Reviewed Original ResearchConceptsTSA cellsWhole cell levelVoltage-dependent activityGuinea pig OHCsOuter hair cell motor proteinMotor proteinsPM domainsMaximum transmembrane potentialPrestin activityMembrane susceptibilityTransmembrane potentialCell membranePrestinTsA201 cellsBiophysical influencesMembrane stiffnessElectroporationCellsBasal portionSignificant resistanceMembrane capacitanceProteinElectromotilityAuditory sensitivitySusceptibilityN-Terminal-Mediated Homomultimerization of Prestin, the Outer Hair Cell Motor Protein
Navaratnam D, Bai JP, Samaranayake H, Santos-Sacchi J. N-Terminal-Mediated Homomultimerization of Prestin, the Outer Hair Cell Motor Protein. Biophysical Journal 2005, 89: 3345-3352. PMID: 16113116, PMCID: PMC1366831, DOI: 10.1529/biophysj.105.068759.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell MembraneCell SeparationCHO CellsCricetinaeDimerizationElectric CapacitanceElectric ConductivityElectrophysiologyFlow CytometryFluorescence Resonance Energy TransferGerbillinaeGreen Fluorescent ProteinsHair Cells, Auditory, OuterMechanotransduction, CellularMembrane PotentialsMicroscopy, ConfocalMicroscopy, FluorescenceModels, BiologicalMolecular Motor ProteinsMolecular Sequence DataMutationProtein BindingProtein ConformationProtein Structure, TertiaryProteinsTransfectionConceptsOuter Hair Cell Motor ProteinStructure-function relationsNormal membrane targetingMammalian cochlear amplificationIntact N-terminusMembrane targetingDomain proteinsMembrane topologyFluorescence resonance energy transferCell mechanical responsePrestin moleculesMembrane motorMotor proteinsN-terminusShort truncationsPrestinResonance energy transferIntracellular terminiAllosteric modulationProteinTerminusCochlear amplificationVoltage sensingHomomultimerizationModified activity
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 capacitanceProtein- and Lipid-Reactive Agents Alter Outer Hair Cell Lateral Membrane Motor Charge Movement
Santos-Sacchi J, Wu M. Protein- and Lipid-Reactive Agents Alter Outer Hair Cell Lateral Membrane Motor Charge Movement. The Journal Of Membrane Biology 2004, 200: 83-92. PMID: 15520906, DOI: 10.1007/s00232-004-0699-2.Peer-Reviewed Original ResearchDetermination of Cell Capacitance Using the Exact Empirical Solution of ∂Y/∂Cm and Its Phase Angle
Santos-Sacchi J. Determination of Cell Capacitance Using the Exact Empirical Solution of ∂Y/∂Cm and Its Phase Angle. Biophysical Journal 2004, 87: 714-727. PMID: 15240504, PMCID: PMC1304394, DOI: 10.1529/biophysj.103.033993.Peer-Reviewed Original Research
2003
Excitation of fluorescent dyes inactivates the outer hair cell integral membrane motor protein prestin and betrays its lateral mobility
Santos-Sacchi J, Zhao HB. Excitation of fluorescent dyes inactivates the outer hair cell integral membrane motor protein prestin and betrays its lateral mobility. Pflügers Archiv - European Journal Of Physiology 2003, 446: 617-622. PMID: 12783229, DOI: 10.1007/s00424-003-1053-8.Peer-Reviewed Original ResearchCl− flux through a non‐selective, stretch‐sensitive conductance influences the outer hair cell motor of the guinea‐pig
Rybalchenko V, Santos‐Sacchi J. Cl− flux through a non‐selective, stretch‐sensitive conductance influences the outer hair cell motor of the guinea‐pig. The Journal Of Physiology 2003, 547: 873-891. PMID: 12562920, PMCID: PMC2342734, DOI: 10.1111/j.1469-7793.2003.00873.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarbenoxoloneCell MembraneChloride ChannelsChloridesCyclooxygenase InhibitorsElectric CapacitanceElectric ConductivityGadoliniumGuinea PigsHair Cells, Auditory, OuterIon Channel GatingMechanotransduction, CellularMembrane PotentialsMercuric ChlorideMicrodialysisNiflumic AcidOctanolsProteinsSulfonic AcidsConceptsOuter hair cell motorLateral membranesVoltage-dependent conformational changesLateral plasma membranePlasma membraneMotor proteinsCell motorProtein transitionsConformational changesRecent identificationPrestinSomatic motilityAllosteric modulationCL sensitivityAnion fluxHair cellsCochlear amplificationAcoustic ratesOuter hair cellsAlternative mechanismComplicated roleMembranePronounced shiftCellsAmplification
2002
Functional motor microdomains of the outer hair cell lateral membrane
Santos-Sacchi J. Functional motor microdomains of the outer hair cell lateral membrane. Pflügers Archiv - European Journal Of Physiology 2002, 445: 331-336. PMID: 12466934, DOI: 10.1007/s00424-002-0928-4.Peer-Reviewed Original ResearchConceptsOperating voltage rangeLateral membranesMammalian inner earOuter hair cell lateral membraneOuter hair cellsMotor proteinsFunctional variationMechanical deformationNeuroepithelial cellsVoltage rangeMicrodomainsWhole cellsMidpoint voltageHair cellsMotor chargeCell characteristicsMembraneCellsNonlinear capacitanceInner earVoltage-dependent changes in specific membrane capacitance caused by prestin, the outer hair cell lateral membrane motor
Santos-Sacchi J, Navarrete E. Voltage-dependent changes in specific membrane capacitance caused by prestin, the outer hair cell lateral membrane motor. Pflügers Archiv - European Journal Of Physiology 2002, 444: 99-106. PMID: 11976921, DOI: 10.1007/s00424-002-0804-2.Peer-Reviewed Original ResearchConceptsMembrane motorHEK cellsOuter hair cellsArea motor modelLateral membrane areaLateral plasma membranePlasma membraneProtein prestinConstant membrane thicknessConformational changesCharge movementMembrane capacitanceMolecular motorsPrestinMembrane surface areaVoltage sensorDeiters' cellsHair cellsCellsExtreme hyperpolarizationMembrane voltageVoltage-dependent changesMembrane area
2001
Temperature dependence of non-linear capacitance in human embryonic kidney cells transfected with prestin, the outer hair cell motor protein
Meltzer J, Santos-Sacchi J. Temperature dependence of non-linear capacitance in human embryonic kidney cells transfected with prestin, the outer hair cell motor protein. Neuroscience Letters 2001, 313: 141-144. PMID: 11682147, DOI: 10.1016/s0304-3940(01)02266-2.Peer-Reviewed Original Research