1、Neuronal Electric Activities神经元的电活动主讲教师 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 PotentialCh
2、apter 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 Permea
3、bilities of Membrane at Rest The Importance of Regulating the External Potassium Concentration CONCLUDING REMARKSCytosol and Extracellular Fluid Water:Its uneven distribution of electrical charge,so H2O is a polar molecule Ions:Salt dissolves readily in water because the charged portions of the wate
4、r molecule have a stronger attraction for the ions than they have for each otherThe Phospholipid Membrane(磷脂膜)The lipids of the neuronal membrane forming:l a barrier to water-soluble ions l 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5Protein These proteins provide routes for ions to cross the neuron
5、al membrane.The resting and action potentials depend on special proteins that span the phospholipid bilayer.Protein Amino AcidsThe Peptide Bond(肽键)and a Polypeptide(多肽)Figure 3.6 Protein StructureThe primary structureThe secondary structureThe tertiary structureThe quaternary structureEach of the di
6、fferent polypeptides contributing to a protein with quaternary structure is called a subunit(亚基).Channel Proteins Channel protein is suspended in a phospholipid bilayer,with its hydrophobic(疏水的)portion inside the membrane hydrophilic(亲水的)ends exposed to the watery environments on either sideFigure 3
7、.7 A Membrane Ion Channel10Two 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(门控特性)Channels with this property can be opened and closed-gated by changes in the local microenvironment of the membraneIon Pumps(离子泵)Ion pumps are enz
8、ymes that use the energy released by the breakdown of ATP to transport certain ions across the membraneChapter 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
9、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 REMARKSTHE MOVEMENT OF IONS A channel across a membrane is like a bridge across a river.A
10、n 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)Diffusion Temperature-dependent random movement of ions and molecules tends to distrib
11、ute 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).15Figure 3.8 Diffusion Driving ions acro
12、ss the membrane by diffusion happens when The membrane possesses channels permeable to the ions There is a concentration gradient across the membraneElectricity 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 particle
13、s.Opposite charges attract and like charges repel.Figure 3.9 The movement of ions influenced by an electrical fieldOpposite charges attract and like charges repelElectricity Two important factors determine how much current(I)will flow:Electrical potential(V,电势)Electrical conductance(g,电导)Electrical
14、conductance Electrical resistance(电阻,R=1/g)Ohms law:I=gVFigure 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 membrane20Diffusion and E
15、lectricity Electrical charged ions in solution on either side of the neuronal membrane.(带电离子溶解在细胞膜两侧的溶液中)Ions can cross the membrane only by protein channel.(离子必须通过离子通道实现跨膜运动)The protein channels can be highly selective for specific ions.(离子通道对离子具有高度的选择性)The movement of any ion through channel depen
16、ds on the concentration gradient and the difference in electrical potential across the membrane.(离子的跨膜运动依赖于膜两侧的浓度梯度和电位差)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
17、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 The membrane potential(膜电位)is the voltage across the neuronal me
18、mbrane at any moment,represented by the symbol mV.Microelectrode (微电极)and mV measurementTHE IONIC BASIS OF THE RESTING MEMBRANE POTENTIAL(静息电位)Establishing Equilibrium Potential(平衡电位)Figure 3.12 Establishing equilibrium in a selectively permeable membraneNo potential differenceVm=0 mVThe diffusional
19、 force=The electrical forceVm=-80 mV20:1Equilibrium potentials The electrical potential difference that exactly balances an ionic concentration gradient is called an ionic equilibrium potential,or simply equilibrium potential (当离子移动所产生的电位差和离子移动所造成的浓度势能差平衡时，不再有离子的净移动，这时膜两侧的电位差称为离子的平衡电位)Generating a s
20、teady electrical potential difference across a membrane requires An ionic concentration gradient Selective ionic permeability25Before moving on to the situation in real neurons,four important points should be made:1.Large changes in membrane potential are caused by minuscule changes in ionic concent
21、rations (仅需要微小的离子浓度改变就可以引起膜电位大幅度的变化)100 mM99.99999mMVm=-80 mVVm=0 mVBefore 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 (膜内外两侧电荷的不同仅仅分布于膜的内外侧面，而不是分布于整个细胞的内外液)Figure
22、3.13(5 nm)Before moving on to the situation in real neurons,four important points should be made:3.Ions are driven across the membrane at a rate proportional to the difference between the membrane potential and the equilibrium potential(离子的跨膜速率与膜电位和平衡电位的差值成正比).Net movement of K+occurs as the membran
23、e potential differed from the equilibrium potential.This difference (Vm-Eion)is called the ionic driving force(离子驱动力).4.If the concentration difference across the membrane is known for an ion,an equilibrium potential can be calculated for that ion(根据某离子膜两侧浓度的差值可以计算该离子的平衡电位).Na+Equilibrium PotentialF
24、igure 3.14 Another example establishing equilibrium in a selectively permeable membraneThe 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
25、internal ion concentrationsPage 64.Box 3.2.Mark F.Bear,et al.ed.Neuroscience:Exploring the Brain.2nd edition.EK=2.303 log ZFRTioKK30Figure 3.15Figure 3.15Approximate ion concentrations on either side of a neuronal membrane.Relative Ion Permeabilities of Membrane at Rest The resting membrane permeabi
26、lity is forty times greater to K+than to Na+The resting membrane potential is 65mVThe Distribution of Ions Across the Membrane Ionic concentration gradients are established by the actions of ions pumps in the neuronal membrane (膜内外两侧的离子浓度梯度的形成依赖于 离子泵的活动)Two important ion pumps:The sodium-potassium p
27、ump(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 Ca2+out of the cytosol across the cell membrane.Figure 3.16Figure 3.16 The sodium-potassium pump.K+K+Na+Na+Figure 4.4Membrane currents and conductances35 The most potas
28、sium 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(孔袢孔袢),which contributes to the selectivity filter that makes the channel permeable mostly to K+ions.The wide world of potassium channelsFigure 3.18Fig
29、ure 3.18A view of the atomic structure of the potassium channel poreThe importance of regulating the external potassium concentrationIncreasing extracellular potassium depolarizes neuronsFigure 3.19The dependence of membrane potential on external potassium concentration.550-65-17Two protective mecha
30、nisms 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.Figure 3.20F
31、igure 3.20Potassium 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.40Chapter 3The Neuronal Membrane at Rest The CAST OF CHEMI
32、CALS 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 Regulat
33、ing the External Potassium Concentration CONCLUDING REMARKSNeuronal 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 PotentialCha
34、pter 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 PO
35、TENTIAL 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 REMARKSMethods of Recording Action Potentials细胞内记录细胞外记录示波器The Ups and D
36、owns 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 mV45Generation 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 membran
37、e of the nerve fibers in the skin is stretched (感觉神经纤维的细胞膜被牵拉)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 b
38、y depolarization of the membrane beyond threshold.The depolarization that causes action potential arises in different ways in different neurons(引起去极化的不同方式):1.Caused by the entry of Na+through specialized ion channels that sensitive to membrane stretching(膜的牵拉)2.In interneurons,depolarization is usua
39、lly caused by Na+entry through channels that are sensitive to neurotransmitters (神经递质的释放)released by other neurons3.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 p
40、otentials 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).The generation of multiple action potentials Continuous depolarizing current Man
41、y action potentials in succession注入电流The firing frequency of action potentials reflects the magnitude of the depolarizing current(频率反应去极化电流的大小)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的一种方式)Though firing frequency increases with the amount of depolarizi
42、ng 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,不可能产生别的动作电位)Relative refractory period(相对不应期)The amount of current required
43、 to depolarize the neuron to action potential threshold is elevated above normal (绝对不应期之后的几个ms,需要比正常更大的阈电流才能爆发动作电位)50Chapter 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 Potenti
44、als 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
45、ACTION POTENTIALS,AXONS,AND DENDRITES CONCLUDING REMARKSTHE 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的)Repolarization is caused by the efflux of potassium ions (复极化是钾离子外流造成的)The Ins and Ou
46、ts 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 pot
47、ential approached ENa.The falling phase The dominant membrane ion permeability to K+K+flow out of the cell until the membrane potential approached EK.The ins and outs and ups and downs of the action potential in an ideal neuron is shown as below:(Fig 4.5)55Chapter 4 The Action Potential PROPERTIES O
48、F 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 Sod
49、ium Channel Voltage-Gated Potassium Channels Putting the Pieces Together ACTION POTENTIAL CONDUCTION Factor influencing conduction velocity ACTION POTENTIALS,AXONS,AND DENDRITES CONCLUDING REMARKSVoltage clamp(电压钳)proves the above theory:The Voltage-Gated Sodium Channel(电压门控的钠离子通道)The protein forms
50、a pore in the membrane that is highly selective to Na+ions(对Na+具有高度的选择性).The pore is opened and closed by changes in the electrical potential of the membrane(Na+通道的开放和关闭具有电压依从性).Sodium channel structure(Na+通道的结构)Created from a single long polypeptide Has 4 distinct domains,numbered I-IV.The four dom
