北大神经生物学3离子通道和神经元的电活动名师优质课获奖市赛课一等奖课件.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,本幻灯片资料仅供参考，不能作为科学依据，如有不当之处，请参考专业资料。,Neuronal Electric Activities神经元电活动,主讲教师 刘风雨 万有,神经科学研究所、神经生物学系,第1页,Neuronal Electric Activities Include:,Rest Potential,(Chapter 3),Action Potential(Chapter 4),Local Potentials,Post-Synaptic Potential,Excitatory Post-Synaptic Potential,Inhibitory Post-Synaptic Potential,End-plate Potential,Receptor Potential,第2页,Chapter 3The Neuronal Membrane at Rest,The CAST OF CHEMICALS,Cytosol and Extracellular Fluid,The Phospholipid Membrane,Protein,The MOVEMENT OF IONS,Diffusion,Electricity,The IONIC BASIS OF RESTING MEMBRANE POTENTIAL,Equilibrium Potential,The Distribution of Ions Across the Membrane,Relative Ion Permeabilities of Membrane at Rest,The Importance of Regulating the External Potassium Concentration,CONCLUDING REMARKS,第3页,Cytosol and Extracellular Fluid,Water:,Its uneven distribution of electrical charge,so H,2,O is a polar molecule,Ions:,Salt dissolves readily in water because the charged portions of the water molecule have a stronger attraction for the ions than they have for each other,第4页,The Phospholipid Membrane(磷脂膜),The lipids of the neuronal membrane forming:,a barrier to water-soluble ions,a barrier to water,头端-极性磷酸盐-亲水,尾端-非极性碳氢化合物,-疏水,5,第5页,Protein,These proteins provide routes for ions to cross the neuronal membrane.,The resting and action potentials depend on special proteins that span the phospholipid bilayer.,第6页,Protein Amino Acids,第7页,The Peptide Bond(肽键)and a Polypeptide(多肽),第8页,Figure 3.6 Protein Structure,The primary structure,The secondary structure,The tertiary structure,The quaternary structure,Each of the different polypeptides contributing to a protein with,quaternary structure is called a,subunit,(,亚基,).,第9页,Channel Proteins,Channel protein is suspended in a phospholipid bilayer,with its,hydrophobic,(疏水),portion inside the membrane,hydrophilic,(亲水),ends exposed to the watery environments on either side,Figure 3.7 A Membrane Ion Channel,10,第10页,Two Properties of Ion Channels,Ion selectivity,(离子选择性),The diameter of the pore,The nature of the R groups lining it,Gating,(门控特征),Channels with this property can be opened and closed-gated by changes in the local microenvironment of the membrane,第11页,Ion Pumps(离子泵),Ion pumps are enzymes that use the energy released by the breakdown of ATP to transport certain ions across the membrane,第12页,Chapter 3The Neuronal Membrane at Rest,THE CAST OF CHEMICALS,Cytosol and Extracellular Fluid,The Phospholipid Membrane,Protein,THE MOVEMENT OF IONS,Diffusion,Electricity,THE IONIC BASIS OF RESTING MEMBRANE POTENTIAL,Equilibrium Potential,The Distribution of Ions Across the Membrane,Relative Ion Permeabilities of Membrane at Rest,The Importance of Regulating the External Potassium Concentration,CONCLUDING REMARKS,第13页,THE MOVEMENT OF IONS,A channel across a membrane is like a bridge across a river.,An open channel,A net movement of ions across the membrane.,Ion movement requires that,external forces,be applied to drive ions across.,Two factors influence ion movement through channels:,Diffusion,(扩散),Electricity,(电势差),第14页,Diffusion,Temperature-dependent random movement of ions and molecules tends to distribute the ions evenly throughout the solution so that there is a net movement of ions from regions of,high concentration,to regions of,low concentration,.This movement is called,diffusion,(扩散),.,A difference in concentration is called a,concentration gradient,(浓度梯度).,15,第15页,Figure 3.8 Diffusion,Driving ions across the membrane by diffusion happens when,The membrane possesses channels,permeable,to the ions,There is a,concentration gradient,across the membrane,第16页,Electricity,Another way to induce a net movement of ions in a solution is to use,an electrical field,(电场),because ions are electrically charged particles.,Opposite charges attract and like charges repel.,第17页,Figure 3.9 The movement of ions influenced by an electrical field,Opposite charges attract and like charges repel,第18页,Electricity,Two important factors determine how much,current(I),will flow:,Electrical potential,(V,电势),Electrical conductance,(g,电导),Electrical conductance,Electrical resistance,(电阻,R=1,/,g),Ohms law:I=gV,第19页,Figure 3.10 Electrical current flow across a membrane,Driving an ion across the membrane electrically requires,The membrane possesses channels,permeable,to the ions,There is a,electrical potential difference,across the membrane,20,第20页,Diffusion and Electricity,Electrical charged ions in solution on either side of the neuronal membrane.,(带电离子溶解在细胞膜两侧溶液中),Ions can cross the membrane only by protein channel.,(离子必须经过离子通道实现跨膜运动),The protein channels can be highly selective for specific ions.(离子通道对离子含有高度选择性),The movement of any ion through channel depends on the,concentration gradient,and the,difference in electrical potential,across the membrane.,(离子跨膜运动依赖于膜两侧,浓度梯度,和,电位差,),第21页,Chapter 3The Neuronal Membrane at Rest,The CAST OF CHEMICALS,Cytosol and Extracellular Fluid,The Phospholipid Membrane,Protein,The MOVEMENT OF IONS,Diffusion,Electricity,The IONIC BASIS OF RESTING MEMBRANE POTENTIAL,Equilibrium Potential,The Distribution of Ions Across the Membrane,Relative Ion Permeabilities of Membrane at Rest,The Importance of Regulating the External Potassium Concentration,CONCLUDING REMARKS,第22页,The,membrane potential,(膜电位)is the voltage across the neuronal membrane at any moment,represented by the symbol,mV,.,Microelectrode,(微电极)and mV measurement,THE IONIC BASIS OF THE RESTING MEMBRANE POTENTIAL(静息电位),第23页,Establishing Equilibrium Potential(平衡电位),Figure 3.12 Establishing equilibrium in a selectively permeable membrane,No potential difference,V,m,=0 mV,The diffusional force=The electrical force,V,m,=-80 mV,20,:1,第24页,Equilibrium potentials,The,electrical potential difference,that exactly balances an,ionic concentration gradient,is called an ionic equilibrium potential,or simply,equilibrium potential,(当离子移动所产生电位差和离子移动所造成浓度势能差平衡时，不再有离子净移动，这时膜两侧电位差称为离子,平衡电位,),Generating a steady electrical potential difference across a membrane requires,An ionic concentration gradient,Selective ionic permeability,25,第25页,Before moving on to the situation in real neurons,four important points should be made:,Large changes in membrane potential are caused by minuscule changes in ionic concentrations,(仅需要微小离子浓度改变就能够引发膜电位大幅度改变),100 mM,99.99999,mM,V,m,=-80 mV,V,m,=0 mV,第26页,Before moving on to the situation in real neurons,four important points should be made:,2.The net difference in electrical charge occurs at the inside and outside surfaces of the membrane,(膜内外两侧电荷不一样仅仅分布于,膜内外侧面,，而不是分布于整个细胞内外液),Figure 3.13,(5 nm),第27页,Before moving on to the situation in real neurons,four important points should be made:,Ions are driven across the membrane at a rate proportional to the difference between the membrane potential and the equilibrium potential(离子跨膜速率与膜电位和平衡电位差值成正比).,Net movement of K,+,occurs as the membrane potential differed from the equilibrium potential.This difference,(V,m,-E,ion,)is called,the ionic driving force,(离子驱动力).,If the concentration difference across the membrane is known for an ion,an equilibrium potential can be calculated for that ion(依据某离子膜两侧浓度差值能够计算该离子平衡电位).,第28页,Na,+,Equilibrium Potential,Figure 3.14 Another example establishing equilibrium in a selectively permeable membrane,第29页,The Nernst Equation,The exact value of,an equilibrium potential,in mV can be calculated using,the Nernst equation,which takes into consideration:,The charge of the ion,The temperature,The ratio of the external and internal ion concentrations,Page 64.Box 3.2.,Mark F.Bear,et al.ed.Neuroscience:Exploring the Brain.2,nd,edition,.,E,K,=2.303,log,30,第30页,Figure 3.15,Figure 3.15,Approximate ion concentrations on either side of a neuronal membrane.,第31页,Relative Ion Permeabilities of Membrane at Rest,The resting membrane permeability is,forty times,greater to K,+,than to Na,+,The resting membrane potential is,65mV,第32页,The Distribution of Ions Across the Membrane,Ionic,concentration gradients,are established by the actions of,ions pumps,in the neuronal membrane,(膜内外两侧,离子浓度梯度,形成依赖于,离子泵,活动),Two important ion pumps:,The sodium-potassium pump,(钠钾泵)is an enzyme that breaks down ATP in the presence of internal Na,+,.,The calcium pump,(钙泵)is an enzyme that actively transports Ca,2+,out of the cytosol across the cell membrane.,第33页,Figure 3.16,Figure 3.16 The sodium-potassium pump.,K,+,K,+,Na,+,Na,+,第34页,Figure 4.4,Membrane currents and conductances,35,第35页,The most potassium channels have,four subunits,that are arranged like the staves of a barrel to form a pore,Of particular interest is a region called,the pore loop,(孔袢),which contributes to,the selectivity filter,that makes the channel permeable mostly to K,+,ions.,The wide world of potassium channels,第36页,Figure 3.18,Figure 3.18,A view of the atomic structure of the potassium channel pore,第37页,The importance of regulating the external potassium concentration,Increasing extracellular potassium depolarizes neurons,Figure 3.19,The dependence of membrane potential on external potassium concentration.,5,50,-65,-17,第38页,Two protective mechanisms in the brain,Blood-brain barrier,(血脑屏障)limits the movement of potassium(and other blood-borne substances)into the extracellular fluid of the brain,Glia,particularly astrocytes,take up extracellular K,+,whenever concentrations rise,as they normally do during periods of neural activity.,第39页,Figure 3.20,Figure 3.20,Potassium spatial buffering by astrocytes.,When brain K,+,o,increases as a result of local neural activity,K,+,enters astrocytes via membrane channels.The extensive network of astrocytic processes helps dissipate the K,+,over a large area.,40,第40页,Chapter 3The Neuronal Membrane at Rest,The CAST OF CHEMICALS,Cytosol and Extracellular Fluid,The Phospholipid Membrane,Protein,The MOVEMENT OF IONS,Diffusion,Electricity,The IONIC BASIS OF RESTING MEMBRANE POTENTIAL,Equilibrium Potential,The Distribution of Ions Across the Membrane,Relative Ion Permeabilities of Membrane at Rest,The Importance of Regulating the External Potassium Concentration,CONCLUDING REMARKS,第41页,Neuronal Electric Activities Include:,Rest Potential(Chapter 3),Action Potential,(Chapter 4),Local Potentials,Post-Synaptic Potential,Excitatory Post-Synaptic Potential,Inhibitory Post-Synaptic Potential,End-plate Potential,Receptor Potential,第42页,Chapter 4 The Action Potential,PROPERTIES OF THE ACTION POTENTIAL,The Ups and Downs of an Action Potentials,Generation of an Action Potential,The Generation of Multiple Action Potentials,THE ACTION POTENTIAL IN THEORY,Membrane Currents and Conductances,The Ins and Outs of Action Potential,THE ACTION POTENTIAL IN REALITY,The Voltage-Gated Sodium Channel,Voltage-Gated Potassium Channels,Putting the Pieces Together,ACTION POTENTIAL CONDUCTION,Factor influencing conduction velocity,ACTION POTENTIALS,AXONS,AND DENDRITES,CONCLUDING REMARKS,第43页,Methods of Recording Action Potentials,细胞内统计,细胞外统计,示波器,第44页,The Ups and Downs of an Action Potentials,上升支,（去极化）,下降支,（复极化）,超射,超极化激活后电位,2 ms,-65 mV,45,第45页,Generation of an action potential,The perception of sharp,pain,when a thumbtack enters your foot is caused by the generation of,action potentials in certain nerve fibers in the skin,:,The thumbtack enters the skin(图钉扎入皮肤),The membrane of the nerve fibers in the skin is stretched,(感觉神经纤维细胞膜被牵拉),Na,+,-permeable channels open.The entry of Na+depolarizes the membrane(Na,+,通道打开，细胞膜产生去极化),The critical level of depolarization that must be crossed in order to trigger an action potential is called,threshold,(阈电位).,Action potential are caused by depolarization of the membrane beyond threshold,.,第46页,The depolarization that causes action potential arises in different ways in different neurons(引发去极化不一样方式):,Caused by the entry of Na+through specialized ion channels that sensitive to,membrane stretching,(膜牵拉),In interneurons,depolarization is usually caused by Na,+,entry through channels that are sensitive to,neurotransmitters,(神经递质释放),released by other neurons,3.In addition to these natural routes,neurons can be depolarized by,injecting electrical current,(注入电流)through a microelectrode,a method commonly used by neuroscientists to study action potentials in different cells.,Applying increasing depolarization to a neuron has no effect until it crosses,threshold,and then“pop”one action potential.For this reason,action potentials are said to be“,all-or-none,”(全或无现象).,第47页,The generation of multiple action potentials,Continuous depolarizing current Many action potentials in succession,注入电流,第48页,The firing frequency of action potentials reflects the magnitude of the depolarizing current(频率反应去极化电流大小),This is one way that,stimulation intensity,is encoded in the nervous system(中枢神经系统编码刺激强度一个方式),第49页,Though firing frequency increases with the amount of depolarizing current,there is a limit to the rate at which a neuron can generate action potentials.,Absolute refractory period,(绝对不应期),Once an action potential is initiated,it is impossible to initiate another for about 1 ms,(动作电位产生后1 ms,不可能产生别动作电位),Relative refractory period,(相对不应期),The amount of current required to depolarize the neuron to action potential threshold is elevated above normal,(绝对不应期之后几个ms,需要比正常更大阈电流才能暴发动作电位),50,第50页,Chapter 4 The Action Potential,PROPERTIES OF THE ACTION POTENTIAL,The Ups and Downs of an Action Potentials,Generation of an Action Potential,The Generation of Multiple Action Potentials,THE ACTION POTENTIAL IN THEORY,Membrane Currents and Conductances,The Ins and Outs of Action Potential,THE ACTION POTENTIAL IN REALITY,The Voltage-Gated Sodium Channel,Voltage-Gated Potassium Channels,Putting the Pieces Together,ACTION POTENTIAL CONDUCTION,Factor influencing conduction velocity,ACTION POTENTIALS,AXONS,AND DENDRITES,CONCLUDING REMARKS,第51页,THE ACTION POTENTIAL IN THEORY,Depolarization,of the cell during the action potential is caused by the influx of sodium ions across the membrane,(去极化是钠离子内流造成),Repolarization,is caused by the efflux of potassium ions,(复极化是钾离子外流造成),第52页,The Ins and Outs of Action Potential,The rising phase,A very large,driving force,on Na,+,(-80-62)mV=-142mV,The membrane,permeability to,Na,+,K,+,Depolarization of the membrane beyond,threshold,membrane sodium channels opened.,This would allow Na,+,to enter the neuron,causing a massive depolarization until the membrane potential approached,E,Na,.,The falling phase,The dominant membrane ion,permeability to K,+,K,+,flow out of the cell until the membrane potential approached,E,K,.,第53页,The ins and outs and ups and downs of the action potential in an ideal neuron is shown as below:(Fig 4.5),第54页,55,第55页,Chapter 4 The Action Potential,PROPERTIES OF THE ACTION POTENTIAL,The Ups and Downs of an Action Potentials,Generation of an Action Potential,The Generation of Multiple Action Potentials,THE ACTION POTENTIAL IN THEORY,Membrane Currents and Conductances,The Ins and Outs of Action Potential,THE ACTION POTENTIAL IN REALITY,The Voltage-Gated Sodium Channel,Vo