2009
Structure of the BK potassium channel in a lipid membrane from electron cryomicroscopy
Wang L, Sigworth FJ. Structure of the BK potassium channel in a lipid membrane from electron cryomicroscopy. Nature 2009, 461: 292-295. PMID: 19718020, PMCID: PMC2797367, DOI: 10.1038/nature08291.Peer-Reviewed Original ResearchConceptsVoltage sensor domainNative membrane environmentMembrane proteinsMembrane environmentChannel voltage-sensor domainElectron cryomicroscopyVoltage-activated potassium channelsSingle-particle electron cryomicroscopyIndividual protein particlesPotassium channelsBK potassium channelsLarge conductance calciumLipid membranesX-ray crystal structureBK channelsStructural studiesProtein particlesProteinCryomicroscopyCrystal structureFormation of crystalsDomainStructureCrystalsChannels
2006
Using cryo-EM to measure the dipole potential of a lipid membrane
Wang L, Bose PS, Sigworth FJ. Using cryo-EM to measure the dipole potential of a lipid membrane. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 18528-18533. PMID: 17116859, PMCID: PMC1693696, DOI: 10.1073/pnas.0608714103.Peer-Reviewed Original ResearchMeSH KeywordsCryoelectron MicroscopyLipid BilayersLiposomesMembrane PotentialsOsmotic PressurePhosphatidylcholinesConceptsDipole potentialLipid membranesPhase-contrast imagingMolecular dynamics calculationsLipid bilayer membranesIon translocation ratesAtomic potentialLipid moleculesLipid monolayersBilayer membranesDynamics calculationsProbe methodSurface potentialAnionsDiphytanoylphosphatidylcholineCationsElectronsImage intensityAbsolute valueMembraneMoleculesConformationLarge permeabilityMonolayersBilayers
1999
Two-Microelectrode Voltage Clamp of Xenopus Oocytes: Voltage Errors and Compensation for Local Current Flow
Baumgartner W, Islas L, Sigworth F. Two-Microelectrode Voltage Clamp of Xenopus Oocytes: Voltage Errors and Compensation for Local Current Flow. Biophysical Journal 1999, 77: 1980-1991. PMID: 10512818, PMCID: PMC1300479, DOI: 10.1016/s0006-3495(99)77039-6.Peer-Reviewed Original Research
1998
Activation of Shaker Potassium Channels
Schoppa N, Sigworth F. Activation of Shaker Potassium Channels. The Journal Of General Physiology 1998, 111: 295-311. PMID: 9450945, PMCID: PMC2222768, DOI: 10.1085/jgp.111.2.295.Peer-Reviewed Original ResearchActivation of Shaker Potassium Channels
Schoppa N, Sigworth F. Activation of Shaker Potassium Channels. The Journal Of General Physiology 1998, 111: 271-294. PMID: 9450944, PMCID: PMC2222764, DOI: 10.1085/jgp.111.2.271.Peer-Reviewed Original ResearchActivation of Shaker Potassium Channels
Schoppa N, Sigworth F. Activation of Shaker Potassium Channels. The Journal Of General Physiology 1998, 111: 313-342. PMID: 9450946, PMCID: PMC2222769, DOI: 10.1085/jgp.111.2.313.Peer-Reviewed Original Research
1996
Impaired slow inactivation in mutant sodium channels
Cummins T, Sigworth F. Impaired slow inactivation in mutant sodium channels. Biophysical Journal 1996, 71: 227-236. PMID: 8804606, PMCID: PMC1233474, DOI: 10.1016/s0006-3495(96)79219-6.Peer-Reviewed Original ResearchConceptsRat skeletal muscle channelsSodium currentProlonged depolarizationSlow inactivationPersistent sodium currentMaximal sodium currentSkeletal muscle channelsMuscle paralysisSkeletal muscle fibersMutant sodium channelsSustained currentHyperkalemic periodic paralysisM mutationPeriodic paralysisSodium channelsMuscle channelsMuscle fibersParalysisFast inactivationWild-type channelsMutant channelsDepolarization
1994
Voltage gating of ion channels
Sigworth F. Voltage gating of ion channels. Quarterly Reviews Of Biophysics 1994, 27: 1-40. PMID: 7520590, DOI: 10.1017/s0033583500002894.Peer-Reviewed Original ResearchConceptsVoltage-gated calcium channelsNerve action potentialsVoltage-gated sodium channelsRelease of hormonesIon channelsVoltage-gated ion channelsCalcium channelsAction potentialsNeurotransmitter releaseMuscle contractionSodium channelsMembrane proteinsCellular signalsVoltage gatingCentral roleHormoneRelease
1993
Substitution of a hydrophobic residue alters the conformational stability of Shaker K+ channels during gating and assembly
McCormack K, Lin L, Sigworth F. Substitution of a hydrophobic residue alters the conformational stability of Shaker K+ channels during gating and assembly. Biophysical Journal 1993, 65: 1740-1748. PMID: 8274662, PMCID: PMC1225901, DOI: 10.1016/s0006-3495(93)81202-5.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiophysical PhenomenaBiophysicsDNA, ComplementaryDrosophilaDrug StabilityFemaleIon Channel GatingMembrane PotentialsMolecular Sequence DataMutagenesis, Site-DirectedOocytesPeptidesPotassium ChannelsProtein ConformationShaker Superfamily of Potassium ChannelsThermodynamicsXenopus laevisConceptsUncharged amino acid residuesLeucine heptad repeatWild-type subunitsPosition 370Large hydrophobic residuesAmino acid residuesSequence motifsConservative substitutionsHeptad repeatHydrophobic residuesVoltage-gated channelsLeucine residuesAcid residuesTertiary structureS4 segmentSpecific hydrophobic interactionsHydrophilic residuesResidue altersChannel subunitsInactivation gatingChannel complexSubunitsConformational stabilityConformational transitionResiduesFunctional expression and purification of a homomeric human alpha 1 glycine receptor in baculovirus-infected insect cells.
Cascio M, Schoppa N, Grodzicki R, Sigworth F, Fox R. Functional expression and purification of a homomeric human alpha 1 glycine receptor in baculovirus-infected insect cells. Journal Of Biological Chemistry 1993, 268: 22135-22142. PMID: 8408073, DOI: 10.1016/s0021-9258(20)80658-9.Peer-Reviewed Original ResearchConceptsInsect cellsGlyR proteinSf9 cellsMembrane protein channelsSf9 insect cellsSodium dodecyl sulfate-polyacrylamide gelsDodecyl sulfate-polyacrylamide gelsSulfate-polyacrylamide gelsWhole cell lysatesHuman kidney cell lineShares sequenceKidney cell lineTransient expressionExpression systemStructural homologyChannel proteinsBiophysical characterizationProtein channelsFunctional channelsFunctional expressionMembrane fractionNative channelsCell surfaceGlycine receptorsChloride channels
1989
Purified, modified eel sodium channels are active in planar bilayers in the absence of activating neurotoxins.
Shenkel S, Cooper E, James W, Agnew W, Sigworth F. Purified, modified eel sodium channels are active in planar bilayers in the absence of activating neurotoxins. Proceedings Of The National Academy Of Sciences Of The United States Of America 1989, 86: 9592-9596. PMID: 2556720, PMCID: PMC298544, DOI: 10.1073/pnas.86.23.9592.Peer-Reviewed Original ResearchPrimary structure and functional expression of a mammalian skeletal muscle sodium channel
Trimmer J, Cooperman S, Tomiko S, Zhou J, Crean S, Boyle M, Kalen R, Sheng Z, Barchi R, Sigworth F, Goodman R, Agnew W, Mandel G. Primary structure and functional expression of a mammalian skeletal muscle sodium channel. Neuron 1989, 3: 33-49. PMID: 2559760, DOI: 10.1016/0896-6273(89)90113-x.Peer-Reviewed Original ResearchConceptsAlpha subunitHomologous domains IAmino acid segmentSodium channelsSkeletal muscle sodium channelsNorthern blot analysisSkeletal muscleMuscle sodium channelsVoltage-sensitive sodium channelsPrimary structureFunctional expressionDomain IAcid segmentNative channelsSynthetic RNAXenopus oocytesRat muscle fibersBlot analysisRat skeletal muscleEel electroplaxRat brainSubunitsMuscle fibersMuscleCDNA
1988
Open channel noise. IV. Estimation of rapid kinetics of formamide block in gramicidin A channels
Heinemann S, Sigworth F. Open channel noise. IV. Estimation of rapid kinetics of formamide block in gramicidin A channels. Biophysical Journal 1988, 54: 757-764. PMID: 2465033, PMCID: PMC1330382, DOI: 10.1016/s0006-3495(88)83013-3.Peer-Reviewed Original ResearchMeSH KeywordsElectric ConductivityFormamidesGramicidinIon ChannelsKineticsMathematicsMembrane PotentialsModels, BiologicalConceptsBiological ion channelsGramicidin A channelsTime resolutionCurrent histogramFast time scaleOpen channel noiseCharacteristic timeNoise measurementsSingle-channel experimentsNoise experimentsDirect measurementTime scalesA channelsSpectral densityBandwidth limitationsCurrentTheoretical approachMeasurementsIon channelsBlocking processChannelsSingle-channel recordingsSingle-channel currentsNoiseDependence
1980
Single Na+ channel currents observed in cultured rat muscle cells
Sigworth F, Neher E. Single Na+ channel currents observed in cultured rat muscle cells. Nature 1980, 287: 447-449. PMID: 6253802, DOI: 10.1038/287447a0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedElectric ConductivityIon ChannelsMembrane PotentialsMicroelectrodesMusclesRatsSodiumThe variance of sodium current fluctuations at the node of Ranvier
Sigworth F. The variance of sodium current fluctuations at the node of Ranvier. The Journal Of Physiology 1980, 307: 97-129. PMID: 6259340, PMCID: PMC1283036, DOI: 10.1113/jphysiol.1980.sp013426.Peer-Reviewed Original ResearchChemical modification reduces the conductance of sodium channels in nerve
Sigworth F, Spalding B. Chemical modification reduces the conductance of sodium channels in nerve. Nature 1980, 283: 293-295. PMID: 6965422, DOI: 10.1038/283293a0.Peer-Reviewed Original ResearchConceptsChemical modificationTrimethyloxonium ionSuch chemical modificationsCarboxyl groupsNegative chargeSuch reagentsTMO treatmentPermeability propertiesReagentsLinear instantaneous current-voltage relationshipSmaller single-channel conductancePropertiesPotent poisonNormal KdIonsModificationSaxitoxinCharge
1977
Sodium channels in nerve apparently have two conductance states
SIGWORTH F. Sodium channels in nerve apparently have two conductance states. Nature 1977, 270: 265-267. PMID: 593345, DOI: 10.1038/270265a0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnuraElectric ConductivityIn Vitro TechniquesMembrane PotentialsRanvier's NodesSodium