2010
Combinatorial Cysteine Mutagenesis Reveals a Critical Intramonomer Role for Cysteines in Prestin Voltage Sensing
Bai JP, Surguchev A, Bian S, Song L, Santos-Sacchi J, Navaratnam D. Combinatorial Cysteine Mutagenesis Reveals a Critical Intramonomer Role for Cysteines in Prestin Voltage Sensing. Biophysical Journal 2010, 99: 85-94. PMID: 20655836, PMCID: PMC2895379, DOI: 10.1016/j.bpj.2010.03.066.Peer-Reviewed Original ResearchConceptsDisulfide bond formationCysteine residuesCysteine residue pairsSingle cysteine residueCysteine mutagenesisTransmembrane proteinSubstitution mutantsSLC26 familyResidue pairsFörster resonance energy transferCharge movementVoltage-dependent charge movementDisulfide interactionsResonance energy transferPrestinProteinMutantsDimer formationResiduesCysteineHair cellsSurface expressionAnion transportersCochlear amplificationWestern blot
2005
N-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 activityGlibenclamide 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
2004
Protein- 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 Research
2003
Cl− 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
2001
Effects of membrane potential and tension on prestin, the outer hair cell lateral membrane motor protein
Santos‐Sacchi J, Shen W, Zheng J, Dallos P. Effects of membrane potential and tension on prestin, the outer hair cell lateral membrane motor protein. The Journal Of Physiology 2001, 531: 661-666. PMID: 11251048, PMCID: PMC2278494, DOI: 10.1111/j.1469-7793.2001.0661h.x.Peer-Reviewed Original ResearchConceptsMembrane tensionMembrane motor proteinMembrane-bound proteinsHuman embryonic kidney cellsLateral plasma membraneEmbryonic kidney cellsMolecular basisPlasma membraneProtein prestinMotor proteinsConformational changesHigh-resolution analysisPrestin activityPrestinKidney cellsMembrane potentialNon-uniform mapping of stress-induced, motility-related charge movement in the outer hair cell plasma membrane
Takahashi S, Santos-Sacchi J. Non-uniform mapping of stress-induced, motility-related charge movement in the outer hair cell plasma membrane. Pflügers Archiv - European Journal Of Physiology 2001, 441: 506-513. PMID: 11212214, DOI: 10.1007/s004240000455.Peer-Reviewed Original ResearchConceptsCell plasma membranePlasma membraneLateral membranesOuter hair cell plasma membraneVoltage-dependent motilityMammalian cochlear amplifierOuter hair cell electromotilityMembrane microdomainsGating currentsHair cell electromotilityTurgor pressureOHC motorMolecular motorsElectromotile responseMembraneMotilityCytoskeletonCharge movementBell-shaped distributionMicrodomainsElectromotilityNon-uniform mappingPronase treatmentCochlear amplifierPronase
1998
Density of motility-related charge in the outer hair cell of the guinea pig is inversely related to best frequency
Santos-Sacchi J, Kakehata S, Kikuchi T, Katori Y, Takasaka T. Density of motility-related charge in the outer hair cell of the guinea pig is inversely related to best frequency. Neuroscience Letters 1998, 256: 155-158. PMID: 9855363, DOI: 10.1016/s0304-3940(98)00788-5.Peer-Reviewed Original ResearchEffects of Lipophilic Ions on Outer Hair Cell Membrane Capacitance and Motility
Wu M, Santos-Sacchi J. Effects of Lipophilic Ions on Outer Hair Cell Membrane Capacitance and Motility. The Journal Of Membrane Biology 1998, 166: 111-118. PMID: 9841736, DOI: 10.1007/s002329900453.Peer-Reviewed Original ResearchEffect of Membrane Tension on Gap Junctional Conductance of Supporting Cells in Corti's Organ
Zhao H, Santos-Sacchi J. Effect of Membrane Tension on Gap Junctional Conductance of Supporting Cells in Corti's Organ. The Journal Of General Physiology 1998, 112: 447-455. PMID: 9758863, PMCID: PMC2229429, DOI: 10.1085/jgp.112.4.447.Peer-Reviewed Original ResearchConceptsTurgor pressureInner ear gap junctionsMembrane tensionPositive turgor pressureProtein kinase inhibitorsGap junctionsOsmotic pressure regulationPipette pressureSupporting cellsInner earMicroM HCochlear homeostasisGap junctional conductanceKinase inhibitorsMechanical forcesCell sizeJunctional conductanceEffects of membrane potential on the voltage dependence of motility‐related charge in outer hair cells of the guinea‐pig
Santos‐Sacchi J, Kakehata S, Takahashi S. Effects of membrane potential on the voltage dependence of motility‐related charge in outer hair cells of the guinea‐pig. The Journal Of Physiology 1998, 510: 225-235. PMID: 9625879, PMCID: PMC2231020, DOI: 10.1111/j.1469-7793.1998.225bz.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementElectric ConductivityGuinea PigsHair Cells, Auditory, OuterMembrane PotentialsPatch-Clamp TechniquesTime FactorsTemperature dependence of outer hair cell nonlinear capacitance
Santos-Sacchi J, Huang G. Temperature dependence of outer hair cell nonlinear capacitance. Hearing Research 1998, 116: 99-106. PMID: 9508032, DOI: 10.1016/s0378-5955(97)00204-9.Peer-Reviewed Original Research
1997
Mapping the distribution of outer hair cell voltage-dependent conductances by electrical amputation
Santos-Sacchi J, Huang GJ, Wu M. Mapping the distribution of outer hair cell voltage-dependent conductances by electrical amputation. Biophysical Journal 1997, 73: 1424-1429. PMID: 9284309, PMCID: PMC1181041, DOI: 10.1016/s0006-3495(97)78174-8.Peer-Reviewed Original ResearchConceptsLateral membranesVoltage magnitudeElectrical techniquesAcoustic frequencyKilohertz rangeOuter hair cell functionVoltage-dependent conductancesVoltage sensorPlasma membraneHair cell functionMechanical effectorsSynaptic poleVoltage-dependent currentsMembrane moleculesAuditory functionDense populationCell functionCable propertiesCochlear amplifierOHC motilitySensory receptors
1996
Effects of Salicylate and Lanthanides on Outer Hair Cell Motility and Associated Gating Charge
Kakehata S, Santos-Sacchi J. Effects of Salicylate and Lanthanides on Outer Hair Cell Motility and Associated Gating Charge. Journal Of Neuroscience 1996, 16: 4881-4889. PMID: 8756420, PMCID: PMC6579298, DOI: 10.1523/jneurosci.16-16-04881.1996.Peer-Reviewed Original ResearchConceptsOuter hair cellsEffects of salicylateConcentration-response curvesGuinea pig outer hair cellsOHC motilityAuditory frequency selectivityForm of salicylateHalf-maximal concentrationReversible tinnitusHearing lossDepolarized levelsHair cell motilityComparable groupsHair cellsOuter Hair Cell MotilityInner aspectOuter aspectSubsurface cisternaeTrypsin treatmentMotilityPressure changesHill coefficientSalicylatePresent experimentsVoltage-induced movement
1994
Motility voltage sensor of the outer hair cell resides within the lateral plasma membrane.
Huang G, Santos-Sacchi J. Motility voltage sensor of the outer hair cell resides within the lateral plasma membrane. Proceedings Of The National Academy Of Sciences Of The United States Of America 1994, 91: 12268-12272. PMID: 7991617, PMCID: PMC45418, DOI: 10.1073/pnas.91.25.12268.Peer-Reviewed Original Research
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 ResearchVoltage-dependent ionic conductances of type I spiral ganglion cells from the guinea pig inner ear
Santos-Sacchi J. Voltage-dependent ionic conductances of type I spiral ganglion cells from the guinea pig inner ear. Journal Of Neuroscience 1993, 13: 3599-3611. PMID: 8393487, PMCID: PMC6576533, DOI: 10.1523/jneurosci.13-08-03599.1993.Peer-Reviewed Original ResearchConceptsType I spiral ganglion cellsSpiral ganglion cellsOutward K currentsGuinea pig inner earGanglion cellsK currentsSpiral ganglion cell somataTTX-sensitive Na currentsInner earGanglion cell somataSpontaneous spike activityWhole-cell voltage clampNa currentIntrinsic membrane propertiesInner hair cellsSingle-unit studiesSingle-unit activityHalf-maximal amplitudeAfferent innervationCochlear nucleusIntrinsic electrical propertiesVoltage-dependent ionic conductancesCell somataExtracellular ionic environmentSpike activity
1991
Reversible inhibition of voltage-dependent outer hair cell motility and capacitance
Santos-Sacchi J. Reversible inhibition of voltage-dependent outer hair cell motility and capacitance. Journal Of Neuroscience 1991, 11: 3096-3110. PMID: 1941076, PMCID: PMC6575435, DOI: 10.1523/jneurosci.11-10-03096.1991.Peer-Reviewed Original ResearchIsolated supporting cells from the organ of Corti: Some whole cell electrical characteristics and estimates of gap junctional conductance
Santos-Sacchi J. Isolated supporting cells from the organ of Corti: Some whole cell electrical characteristics and estimates of gap junctional conductance. Hearing Research 1991, 52: 89-98. PMID: 2061216, DOI: 10.1016/0378-5955(91)90190-k.Peer-Reviewed Original ResearchConceptsInput resistanceWhole-cell voltage clamp studiesAverage input resistanceHensen's cellsOrgan of CortiVoltage-clamp studiesGuinea pig organJunctional resistanceClamp studiesCell levelPig organsSingle-cell levelGap junctional conductanceG omegaElectrical activityExternal TEACell couplingCortiJunctional conductanceCellsOrgansSensitive indicatorSmall groupCell values
1989
Asymmetry in voltage-dependent movements of isolated outer hair cells from the organ of Corti
Santos-Sacchi J. Asymmetry in voltage-dependent movements of isolated outer hair cells from the organ of Corti. Journal Of Neuroscience 1989, 9: 2954-2962. PMID: 2769373, PMCID: PMC6569687, DOI: 10.1523/jneurosci.09-08-02954.1989.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomechanical PhenomenaCell MovementCell SeparationElectric ConductivityElectrophysiologyGuinea PigsHair Cells, AuditoryOrgan of CortiConceptsOuter hair cellsWhole-cell voltage-clamp techniqueHair cellsNormal resting potentialsOrgan of CortiVoltage-clamp techniqueCell shorteningAcoustic stimulationReceptor potentialResting potentialsResponse magnitudeOHC movementsReported productionStimulationHyperpolarizationComparable levelsNeural tuningCell length changesDepolarizationLength changesCellsBasilar membraneVoltage stimulation