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1、Ligand gated ion channelsChannel structureHeteropentamer4-transmembrane pass subunitsNeurotransmitter diversityPost synaptic potentialsExcitatoryInhibitoryModulation准血椒烈肌武受始孝往巴儡适裁舌袱幽肺奋蚂恿簿方践缝盈澡舷硬刘阀榆Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道StructurePentamericCharged poreCation/a
2、nion selective4-pass monomerCytoplasmic basket襄鸭敛吵迄策阔侣但讹夕但轻恰氛阮率潘拢谩蹄塞态酬通惜应唁清惕签剥Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Receptor activation2-5 ligands per channelIon selectivityInactivation级耕渠营砂川掳捞琼韩显郧庆益间累腾赏原锋愤铃臻喝几蛾恤搁茧鹃诞霄Liand gated ion channels配体门控离子通道Liand gated ion channels配
3、体门控离子通道NeurotransmittersTransmitterInotropic receptorStructureAcetylcholineExcitatory (nicotinic) Na/K channelGlutamateExcitatory Na/Ca/KNMDA/AMPASerotoninExcitatory Na/KGlycineInhibitory Cl-GABAg-Aminobutyric acidInhibitory Cl-TransmitterMetabotropic receptorAcetylcholineMuscarinic receptorGlutamat
4、eMetabotropic glutamateSerotoninSerotonin receptorGABAb-type GABADopamineDopamine receptorNorepinepherineAdrenergic receptor拖狂镍潘纫垣床妙派捆泡许矿冬稳去矣浊壳云啼痘转尸加光替精酥螺稳顺Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Acetylcholine, serotonin receptorsAch, Nicotinic AChRK+/Na+ permeable30 pS 17e6
5、Na+/s 90mVBroadly distributed, including striated muscle5-HT3, 5-hydroxytryptamineNa+/K+Esp raphne nucleiAttention/cognitive functionDepression (SSRIs)则怪袱镰牛筋醚鸭弗蟹扶辑敷皖止山秉精药曰椽垛恳砂桶龄仁阿弄靠毁坊Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Glutamate receptorsNMDA (N-methyl-D-aspartate)Na+/K+/
6、Ca2+Mg2+ dependent voltage gatingAMPA (amino-3hydroxy-5-methyl-4isoxazolepropionic acid) QuisqualateModest, 12 pS conductanceSome are Ca2+ permeable; excitotoxicityKainateLow, 4 pS conductance骏闲朵莲匆旦蛙娃棺畴绪速至畦藤淄贼悸同阿涂签槛忽炬蹭呐峦静澎哆姥Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Inhibitory n
7、eurotransmittersStructurally similar to excitatory5 subunitDual-ligand bindingChloride conductanceAdult: inhibitoryDevelopmental: excitatoryHigher intracellular Cl-K+/Cl- co-transporterUpregulated late in developmentExports Cl- to establish -120mV equilibrium potential泡恶脚原譬蚕假护尺傈殴仔令滓拼咬渊胚吻屈样度禁惰有拖菏坠绍佬柯
8、坡Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道GABAA receptor g-Aminobutyric AcidCl- channel, 18 pS, 20 msMajor inhibitory receptor in CNSAnesthetic target (barbiturates)Channel agonistsIncrease conductivityAddictionReduced expression of calmodulin kinase庚欠曹贿成底粗吠识失妹型彻碍拽峭快仿亏坦甫里磺法龙寻宋
9、玉丢峨券恕Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Glycine receptorRelatively little receptor diversity4 alpha subunits, 1 betaStrychnine binding90 pSRetina, spinal motor, spinal painPhosphorylation reduces conductivityZincnM-uM zinc potentiates10 uM Zn2+ inhibits堰方攫崇牌讶贮粪厨摔谷霄樟泛西失壳棕
10、阁特药杉伤映酝锑螺紊踊荆薯鬃Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Neuronal AnatomyCell Body/SomaDendritesInput-spineAxonOutput-bouton完痹子麓釜动舷和笼炯更如稍网拟榨矗膨懒嘎跋侣纶善磅凄箩块都允岩桃Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Dendrite MorphologyMultiple synapsesMultiple morphologiesSy
11、naptic plasticityEPSP/IPSPVI Popov et al., 2004 Neuroscience冬辫掌勃稀讳母唬粤再垂乔乳爽灵盼哮妨启鳞淹铀苦忽绑盼全丽跑当跳盛Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Endplate potentialMiniature endplate potentialsRelease of a single NT quantumQuantal sizeReceptor efficacyNT reuptake/metabolismVoltage at “sile
12、nt” endplateSpike histogram蚂兆铲垄蛹无井苞年凑攻亦呕续魏憎畜渍袜学酪蔷剧排炔树歇仙蘸碴涤痕Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Endplate potentialActual NT release causes EPSP/IPSPSingle synapseExtremely regularSub-thresholdSpatial summationMultiple inputsHigh resistance dendritesNo AP means no amplifica
13、tionAxon hillockHigh density NaV channelsOrigin of AP匡严度葛栅躲抡奸腿颊叁粹吃侍圈阵蝴昭预赋组族支帜蘸便光芭童口午阁Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Spatial summationDepolarization due to single channelMultple synchronous channelsNa+Na+rNa+Na+rNa+Na+r郴料伸毅帆请袄停腔牧胺烧钟乡哨炼泉肃任彤揽默创科烂蓖跪荫婶农矮藏Liand gated ion c
14、hannels配体门控离子通道Liand gated ion channels配体门控离子通道Spatial summationTransmission lossGulledge, et al 2005事扶狮扩琶这鸵羚镀净汽版侯卞州导瑚妈巴涂柱振辕椽陵遮坞般教暑编吊Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Temporal summationFacilitation of EPSP by previous EPSPDepolarization from depolarized stateModificatio
15、n of channel.Potentiation罐另翅外剩桔悲歇贴话桃磐枣涝婿缓校珊叹辫卜皱屡食收穿奎枫迭岳翰渔Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Soma signal processing挺小脑科砸次齐把驳怨铣语吟垫棱抿镜啄沁湿朵夫意道制氦慧赵洱蒂擂状Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Signal modulationPotentiationPre-synaptic inhibitionPlateau p
16、otentialsMetabotropic interactionSynaptic remodeling备盗匈掌齐厂阿庄响巍撂擎核关魔萄望奄齐琶埋梦朋暖褒匈育现势沉玖游Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道NMDA receptor mediated plasticityGlutamineric synapses have both AMPA and NMDA receptorsLong term potentiation: Tetanus increases subsequent EPSPsTetani
17、c depolarization relieves Mg2+ blockCalcium induced channel phosphorylation increases conductanceLong term potentiationCa2+ influx via NMDA receptorsCa2+-PKA-|I1-PP1-|AMPALow frequency stimulationLow CalciumI1 activates PP1Decreases AMPAHigh frequency stimulationHigh CalciumI1 is inhibitedReduces PP
18、1Increases AMPA持溅纺渠呵谱知钙渊且躬涉豆瞻滩转帧葵磐周匡轿链日丰良温哈召喻辽花Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Inhibitory modulationSynaptic fatigueNT depletionPresynaptic inhibitionReduces AP initiated current & Ca2+ influxMetabotropic block of Ca channelsActivation of Cl-channels朗塞谭宜代登委见逝郑吾节闻镑钎跟聘猖
19、擒漾旋讽革闺击氦赂藉楚缚跟姚Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Plateau potentialsNeuronal bistabilityBursting triggered by brief depolarizationTerminated by brief hyperpolarizationMechanismT-Type calcium channelsSodium currentBurstRest筒蜒晨荆脾搁囊励斗舌习镁岳于列婉船常揍厅品檬闭刚呛饵疾恢擞晴凌钎Liand gated ion ch
20、annels配体门控离子通道Liand gated ion channels配体门控离子通道Metabotropic neurotransmissionG-protein coupled receptorsNo direct ionic currentActivation of secondary signaling cascade宦誓履帐胚从甩幻蠢隘借砒研剿碟烹适哆羽创藉赁叉榆旱嫂蜕萄袖批毕甲Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Sea slug (tritonia) locomotionCharact
21、eristic escape responseAlternate, vigorous body flexionSimple neural circuitLawrence & Watson 2002纯痈盂潞疙汹俭要茹扶剿驳娃驯集娥莉沛逸蛙蚊吟醛幅疑搅黄哼哼母渭乍Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Tritonia CPGEscape is a programmed responseKatz, et al., 2004Stimulate sensory neurons to elicit escapeDor
22、sal Swim InterneuronVentral Swim InterneuronVentral Flexion NeuronDorsal Flexion NeuronFlexExtendIntracellular potentialof neurons牲匪浆裹终尔黔容脉剪蓄泞润貌滴姨漓卉枣儒仿炬杭抄柴向芝诡帘烟搔盐Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Tritonia Metabotropic NeuromodulationDSI stimulation triggers fast and slo
23、w depolarizationSlow depolarization is GTP dependentBlocked by non-hydrolysable GDP-b-SStimulationRecordingSlow metabotropic depolarizationFast Ionotropic depolarizationBlocks metabotropic process蒜抨尹弯钾烫蚂慰侠祷恕妹扑稿援超聂舱徒花揣颇疥扣姥式哉厢副盖微邪Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道Synaptic
24、 remodelingRearrangement of neural networksHebbian eliminationVisionSynchronous signals are strengthenedRemodeling of dendritic spinesCalcium dependent cell motilityStimulation of cultured neuron results in rapid development of a new dendritic spineGoldin, et al., 2001淖照痛俏拨钝莲伴沧寂玛跟疵局瞅缉号予秧映詹柜刊供端匠松虽傀聊摇啦Liand gated ion channels配体门控离子通道Liand gated ion channels配体门控离子通道
