1Physics 208 Guest LectureSept. 29, 2006Membrane Ion Channels Ching KungLaboratory of Molecular Biologyand Department of GeneticsGroupOrganismOrganTissueCellMoleculeAnimalBrainNervous tissueNeuronIon channelsElectricity outside the organismElectricity in an organ (outside the cells)AnimalBrainNervous tissueNeuronIon channels2 ion channelsIon ChannelsLipid bilayeroutinOutline1. Chemistry Review: ions and water the lipid membrane2. Action Potential: its ionic basis3. The activities of ion channels4. The structure of ion channelsa. filtration b. gating3E.g.Na atomNa+ ionelectron+Na+ ion+K+ ion+Ions differ in being + or -, number of charges (2+, 3+ etc.)but also differ in size.Na+ ChannelsLipid bilayeroutinNa+K+ ChannelsWater is polarOHH+-a dipoleWater associates with and forms a shell around ions.K+the O- of H2O4phospholipidheadfatty acid tail- c - c - c - c - … H H H H H H H Hnon-chargedhydrocarbon= oilEssentially oilwaterwaternonpolarpolarpolarCan associate withother charges, e.g. ionsCannotThe cell membrane insulates and ion concentrations in/outcan be different.X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+X+Key ions in cell biology: K+, Na+, and Ca2+. Also H+, Cl-. Distribution:K+ Na+ Ca2+K+ Na+ Ca2+cellmembraneKey ions in cell biology: K+, Na+, and Ca2+. Also H+, Cl-. Distribution:K+K+cellmembraneNa+Na+outin5outinoutinEK+ENa+EK+ + ENa+ = membrane potential= -100 mV (inside negative) at restOutline1. Chemistry Review: ions and water the lipid membrane2. Action Potential: its ionic basis3. The activities of ion channels4. The structure of ion channelsa. filtration b. gatingR. Descartes(1596-1650)6Action Potentials:The digital codesof the nervous system.restingpotentialactionpotentiala depolarization(beyond zero)a repolarizationa depolarization(beyond zero)outEK+ENa+++Na+ channels openoutina repolarizationoutEK+ENa+--7outinNa+ channels closeK+ channels open Outline1. Chemistry Review: ions and water the lipid membrane2. Action Potentials: its ionic basis3. The activities of ion channels4. The structure of ion channelsa. filtration b. gatingIon ChannelsLipid bilayeroutinChannels outin++closed openIon Registering Ion-channel activitiesExtracellular recordingIntracellular recording (1930’s)Voltage clamp Patch clamprestingpotentialactionpotential8Registering Ion-channel activitiesExtracellular recordingIntracellular recordingVoltage clamp (1949, NP 1955) Patch clamp1991 Nobel Prize in Medicine.The Patch-Clamp MethodChannels outin++closed openIon The Patch-Clamp MethodSingle-channelactivitiesopen closed31000macroscopicmicroscopic9The nanoSiemens MS unitary conductance of E. coliMartinac et al. (1987) PNAS 84: 2297.Outline1. Chemistry Review: ions and water the lipid membrane2. Action Potential: its ionic basis3. The activities of ion channels4. The structure of ion channelsa. filtration b. gatingNa+ inK+ outfastspecificoutEK+ENa+++Very small resistanceoutin10Doyle et al. (1998) Science 280: 69.2003 Nobel Prize in ChemistryA transmembrane protein= 3.4 nm~ 10 µm310-9 m10-6 mDoyle et al. (1998) Science 280: 69.Zhou et al., (2001) Nature 414: 43.In solution, K+ is hydrated.There is no energetic cost in changingthe hydration shell.11Equally costless.Na+Na+Ditto for Na+.H20Na+ channelEnergetic cost for Na+ to enter K+ channel.Na+Na+fast: 106 ions /secspecific: PK : Pna > 50 : 1Ion Channels outinclosed opengoverned by a factor (stimulus)gate12O CLong et al. (2005) Science 309: 897.Stimulus can be a ligandheat voltage force++- -- -++AnimalBrainNervous tissueNeuronIon
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