离子通道和神经元的电活动PPT课件

1、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1页/共80页Chapter 3The Neuronal Membrane at Rest The CAST O

2、F 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

3、Regulating the External Potassium Concentration CONCLUDING REMARKS第2页/共80页Cytosol 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 water molecule have a stronger attractio

4、n for the ions than they have for each other第3页/共80页The 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5第4页/共80页Protein These proteins provide routes for ions to cross the neuronal membrane.The res

5、ting and action potentials depend on special proteins that span the phospholipid bilayer. 第5页/共80页Protein Amino Acids第6页/共80页The Peptide Bond (肽键) and a Polypeptide (多肽)第7页/共80页Figure 3.6 Protein StructureThe primary structureThe secondary structureThe tertiary structureThe quaternary structureEach

6、of the different polypeptides contributing to a protein with quaternary structure is called a subunit (亚基).第8页/共80页Channel ProteinsChannel 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

7、on either sideFigure 3.7 A Membrane Ion Channel10第9页/共80页Two Properties of Ion ChannelsIon selectivity (离子选择性) The diameter of the pore The nature of the R groups lining itGating (门控特性) Channels with this property can be opened and closed-gated by changes in the local microenvironment of the membran

8、e第10页/共80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11页/共80页Chapter 3The Neuronal Membrane at Rest THE CAST OF CHEMICALS Cytosol and Extracellular Fluid The Phospholipid Membrane Protein THE MOVEMENT OF ION

9、S 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12页/共80页THE MOVEMENT OF IONS A

10、 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13页/共80页Diffusion

11、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

12、 called a concentration gradient (浓度梯度).15第14页/共80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15页/共80页Electricity Another way to induce a net movement of i

13、ons 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16页/共80页Figure 3.9 The movement of ions influenced by an electrical fieldOpposite charges attract and like charges repel第17页/共80页Electricity Two imp

14、ortant 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18页/共80页Figure 3.10 Electrical current flow across a membrane Driving an ion across the membrane electrically

15、 requires The membrane possesses channels permeable to the ions There is a electrical potential difference across the membrane20第19页/共80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的溶液中) Ions can cross the membrane only by prote

16、in 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 depends 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)第20页/共80页Chapter 3The

17、 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 o

18、f Membrane at Rest The Importance of Regulating the External Potassium Concentration CONCLUDING REMARKS第21页/共80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 measurementTHE IONIC BASIS OF THE RESTING

19、 MEMBRANE POTENTIAL (静息电位)第22页/共80页Establishing Equilibrium Potential (平衡电位)Figure 3.12 Establishing equilibrium in a selectively permeable membraneNo potential differenceVm = 0 mVThe diffusional force = The electrical forceVm = - 80 mV20:1第23页/共80页Equilibrium potentials The electrical potential dif

20、ference 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 steady electrical potential difference across a membrane requires An ionic concentration g

21、radient Selective ionic permeability25第24页/共80页Before 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 concentrations (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 mV第25页/共

22、80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 3.13(5 nm)第26页/共80页Before moving on to the situation in real ne

23、urons, 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 membrane potential differed from the equilibrium potential

24、. 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).第27页/共80页 Na+ Equilibrium PotentialFigure 3.14 Another example establ

25、ishing equilibrium in a selectively permeable membrane第28页/共80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 concentra

26、tionsPage 64. Box 3.2. Mark F. Bear, et al. ed. Neuroscience: Exploring the Brain. 2nd edition. EK = 2.303 log ZFRTioKK30第29页/共80页Figure 3.15Figure 3.15Approximate ion concentrations on either side of a neuronal membrane.第30页/共80页Relative Ion Permeabilities of Membrane at Rest The resting membrane p

27、ermeability is forty times greater to K+ than to Na+ The resting membrane potential is 65mV第31页/共80页The Distribution of Ions Across the Membrane Ionic concentration gradients are established by the actions of ions pumps in the neuronal membrane (膜内外两侧的离子浓度梯度的形成依赖于 离子泵的活动) Two important ion pumps: Th

28、e 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 Ca2+ out of the cytosol across the cell membrane.第32页/共80页Figure 3.16Figure 3.16 The sodium-potassium pump.K+K+Na+Na+第33页/共80页Figure 4.4Membran

29、e currents and conductances35第34页/共80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+ i

30、ons.The wide world of potassium channels第35页/共80页Figure 3.18Figure 3.18A view of the atomic structure of the potassium channel pore第36页/共80页The importance of regulating the external potassium concentrationIncreasing extracellular potassium depolarizes neuronsFigure 3.19The dependence of membrane pot

31、ential on external potassium concentration.550-65-17第37页/共80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+ wheneve

32、r concentrations rise, as they normally do during periods of neural activity.第38页/共80页Figure 3.20Figure 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 process

33、es helps dissipate the K+ over a large area.40第39页/共80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 Dis

34、tribution of Ions Across the Membrane Relative Ion Permeabilities of Membrane at Rest The Importance of Regulating the External Potassium Concentration CONCLUDING REMARKS第40页/共80页Neuronal Electric Activities Include: Rest Potential (Chapter 3) Action Potential (Chapter 4) Local Potentials Post-Synap

35、tic Potential Excitatory Post-Synaptic Potential Inhibitory Post-Synaptic Potential End-plate Potential Receptor Potential第41页/共80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

36、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 conduc

37、tion velocity ACTION POTENTIALS, AXONS, AND DENDRITES CONCLUDING REMARKS第42页/共80页Methods of Recording Action Potentials细胞内记录细胞外记录示波器第43页/共80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 mV45第44页/共80页Generation of an action potential The perception of sharp pain when a

38、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 (感觉神经纤维的细胞膜被牵拉) Na+-permeable channels open. The entry of Na+ depolarizes the membrane (Na

39、+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45页/共80页The depolarization that causes action potential arises in different way

40、s 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 usually caused by Na+ entry through channels that are sensitive to neurotransmitters (神经递质的释放) released by other neurons3

41、. 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 th

42、reshold, and then “pop” one action potential. For this reason, action potentials are said to be “all-or-none” (全或无现象).第46页/共80页The generation of multiple action potentials Continuous depolarizing current Many action potentials in succession注入电流第47页/共80页The firing frequency of action potentials refle

43、cts 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)第48页/共80页Though firing frequency increases with the amount of depolarizing current, there is a limit to the rate at which a neuron can generate a

44、ction 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 to depolarize the neuron to action potential threshold is eleva

45、ted 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)50第49页/共80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 a

46、nd 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 REM

47、ARKS第50页/共80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的) Repolarization is caused by the efflux of potassium ions (复极化是钾离子外流造成的)第51页/共80页The Ins and Outs of Action Potential The rising

48、 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

49、Na. The falling phase The dominant membrane ion permeability to K+ K+ flow out of the cell until the membrane potential approached EK.第52页/共80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53页/共80页55第54页/共80页Chapter 4 The Action Potential

50、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 Volta

51、ge-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55页/共80页Voltage clamp (电压钳) proves the above theory:第56页/共80页The Voltage-Gated Sodium Cha

52、nnel(电压门控的钠离子通道) The protein forms 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).第57页/共80页Sodium channel structure(Na+ 通道的结构) Created from a single long polypeptide

53、 Has 4 distinct domains, numbered I-IV. The four domains are believed to clump together to form a pore between them Each domain consists of 6 transmembrane alpha helices, numbered S1-S6 The channel has pore loops that are assembled into a selectivity filter60第58页/共80页Figure 4.6Structure of the volta

54、ge-gated sodium channel(a) How the sodium channel polypeptide chain is believed to be woven into the membrane. The molecule consists of four domains, I-IV. Each domain consists of 6 alpha helices, which pass back and forth across the membrane第59页/共80页Figure 4.6(b) An expanded view of one domain show

55、ing the voltage sensor of alpha helix S4 and the pore loop (red), which contributes to the selectivity filter(c) A view of the molecule showing how the domains may arrange themselves to form a pore between them.电压感受器第60页/共80页Figure 4.7When the membrane is depolarized to threshold, the molecule twist

56、s into a configuration that allows the passage of Na+ through the pore.The voltage sensor resides in segment S4 of the molecule. In this segment, positively charged amino acid residues are regularly spaced along the coils of the helix. Thus, the entire segment can be forced to move by changing the m

57、embrane potential. Depolarization pushes S4 away from the inside of the membrane, and this conformational change in the molecule causes the gate to open.第61页/共80页The patch-clamp (膜片钳) Method- 40 mV65第62页/共80页Functional properties of the sodium channel (Na+ 通道的功能)1.They open with little delay2.They s

58、tay open for about 1 ms and then close (inactivate)3.They cannot be opened again by depolarization until the membrane potential returns to 65 mV关闭开放失活去失活第63页/共80页Functional properties of the sodium channelFigure 4.9 (c) A model for how changes in the conformation of the sodium channel protein might

59、yield its functional properties.1.The closed (关闭) channel; 2. Opens (开放) upon membrane depolarization;3. Inactivation (失活) occurs when a globular portion of the protein swings up and occludes the pore; 4. Deinactivation (去失活) occurs when the globular portion swings away and the pore closes by moveme

60、nt of the transmembrane domains关闭开放失活去失活第64页/共80页Toxins on the sodium channel Tetrodotoxin (TTX, 河豚毒素) and saxitoxin Channel-blocking toxin Batrachotoxin, veratridine and aconitine Open the channels inappropriately Open at more negative potentials Open much longer than usual第65页/共80页Putting the Piec