離子通道和神經(jīng)元的電活動PPT課件

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頁/共80頁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頁/共80頁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頁/共80頁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頭端-極性磷酸鹽-親水尾端-非極性碳?xì)浠衔?疏水5第4頁/共80頁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頁/共80頁Protein Amino Acids第6頁/共80頁The Peptide Bond (肽鍵) and a Polypeptide (多肽)第7頁/共80頁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 (亞基).第8頁/共80頁Channel ProteinsChannel protein is suspended in a phospholipid bilayer, with its hydrophobic (疏水的) portion inside the membrane hydrophilic (親水的) ends exposed to the watery environments

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

8、e第10頁/共80頁Ion Pumps (離子泵)Ion pumps are enzymes that use the energy released by the breakdown of ATP to transport certain ions across the membrane第11頁/共80頁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頁/共80頁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 (擴散) Electricity (電勢差)第13頁/共80頁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 (擴散). A difference in concentration is

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

13、ons in a solution is to use an electrical field (電場), because ions are electrically charged particles. Opposite charges attract and like charges repel.第16頁/共80頁Figure 3.9 The movement of ions influenced by an electrical fieldOpposite charges attract and like charges repel第17頁/共80頁Electricity Two imp

14、ortant factors determine how much current (I) will flow: Electrical potential (V, 電勢) Electrical conductance (g, 電導(dǎo)) Electrical conductance Electrical resistance (電阻, R=1/g) Ohms law: I = gV第18頁/共80頁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頁/共80頁Diffusion and Electricity Electrical charged ions in solution on either side of the neuronal membrane. (帶電離子溶解在細(xì)胞膜兩側(cè)的溶液中) Ions can cross the membrane only by prote

16、in channel. (離子必須通過離子通道實現(xiàn)跨膜運動) The protein channels can be highly selective for specific ions. (離子通道對離子具有高度的選擇性) The movement of any ion through channel depends on the concentration gradient and the difference in electrical potential across the membrane. (離子的跨膜運動依賴于膜兩側(cè)的濃度梯度和電位差)第20頁/共80頁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頁/共80頁 The membrane potential (膜電位) is the voltage across the neuronal membrane at any moment, represented by the symbol mV. Microelectrode (微電極) and mV measurementTHE IONIC BASIS OF THE RESTING

19、 MEMBRANE POTENTIAL (靜息電位)第22頁/共80頁Establishing Equilibrium Potential (平衡電位)Figure 3.12 Establishing equilibrium in a selectively permeable membraneNo potential differenceVm = 0 mVThe diffusional force = The electrical forceVm = - 80 mV20:1第23頁/共80頁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 (當(dāng)離子移動所產(chǎn)生的電位差和離子移動所造成的濃度勢能差平衡時，不再有離子的凈移動，這時膜兩側(cè)的電位差稱為離子的平衡電位) Generating a steady electrical potential difference across a membrane requires An ionic concentration g

21、radient Selective ionic permeability25第24頁/共80頁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 (僅需要微小的離子濃度改變就可以引起膜電位大幅度的變化)100 mM99.99999mMVm = - 80 mVVm = 0 mV第25頁/共

22、80頁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 (膜內(nèi)外兩側(cè)電荷的不同僅僅分布于膜的內(nèi)外側(cè)面，而不是分布于整個細(xì)胞的內(nèi)外液)Figure 3.13(5 nm)第26頁/共80頁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 (離子的跨膜速率與膜電位和平衡電位的差值成正比).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 (離子驅(qū)動力).4.If the concentration difference across the membrane is known for an ion, an equilibrium potential can be calculated for that ion (根據(jù)某離子膜兩側(cè)濃度的差值可以計算該離子的平衡電位).第27頁/共80頁 Na+ Equilibrium PotentialFigure 3.14 Another example establ

25、ishing equilibrium in a selectively permeable membrane第28頁/共80頁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頁/共80頁Figure 3.15Figure 3.15Approximate ion concentrations on either side of a neuronal membrane.第30頁/共80頁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頁/共80頁The Distribution of Ions Across the Membrane Ionic concentration gradients are established by the actions of ions pumps in the neuronal membrane (膜內(nèi)外兩側(cè)的離子濃度梯度的形成依賴于 離子泵的活動) Two important ion pumps: Th

28、e sodium-potassium pump (鈉鉀泵) is an enzyme that breaks down ATP in the presence of internal Na+. The calcium pump (鈣泵) is an enzyme that actively transports Ca2+ out of the cytosol across the cell membrane.第32頁/共80頁Figure 3.16Figure 3.16 The sodium-potassium pump.K+K+Na+Na+第33頁/共80頁Figure 4.4Membran

29、e currents and conductances35第34頁/共80頁 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頁/共80頁Figure 3.18Figure 3.18A view of the atomic structure of the potassium channel pore第36頁/共80頁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頁/共80頁Two protective mechanisms in the brain Blood-brain barrier (血腦屏障) 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頁/共80頁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頁/共80頁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頁/共80頁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頁/共80頁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頁/共80頁Methods of Recording Action Potentials細(xì)胞內(nèi)記錄細(xì)胞外記錄示波器第43頁/共80頁The Ups and Downs of an Action Potentials上升支（去極化）下降支（復(fù)極化）超射超極化激活后電位2 ms- 65 mV45第44頁/共80頁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 (圖釘扎入皮膚) The membrane of the nerve fibers in the skin is stretched (感覺神經(jīng)纖維的細(xì)胞膜被牽拉) Na+-permeable channels open. The entry of Na+ depolarizes the membrane (Na

39、+通道打開，細(xì)胞膜產(chǎn)生去極化) The critical level of depolarization that must be crossed in order to trigger an action potential is called threshold (閾電位). Action potential are caused by depolarization of the membrane beyond threshold.第45頁/共80頁The depolarization that causes action potential arises in different way

40、s in different neurons (引起去極化的不同方式):1.Caused by the entry of Na+ through specialized ion channels that sensitive to membrane stretching (膜的牽拉)2.In interneurons, depolarization is usually caused by Na+ entry through channels that are sensitive to neurotransmitters (神經(jīng)遞質(zhì)的釋放) released by other neurons3

41、. In addition to these natural routes, neurons can be depolarized by injecting electrical current (注入電流) 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” (全或無現(xiàn)象).第46頁/共80頁The generation of multiple action potentials Continuous depolarizing current Many action potentials in succession注入電流第47頁/共80頁The firing frequency of action potentials refle

43、cts the magnitude of the depolarizing current (頻率反應(yīng)去極化電流的大小)This is one way that stimulation intensity is encoded in the nervous system (中樞神經(jīng)系統(tǒng)編碼刺激強度的一種方式)第48頁/共80頁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 (絕對不應(yīng)期) Once an action potential is initiated, it is impossible to initiate another for about 1 ms (動作電位產(chǎn)生后1 ms, 不可能產(chǎn)生別的動作電位) Relative refractory period (相對不應(yīng)期) The amount of current required to depolarize the neuron to action potential threshold is eleva

45、ted above normal (絕對不應(yīng)期之后的幾個ms, 需要比正常更大的閾電流才能爆發(fā)動作電位)50第49頁/共80頁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頁/共80頁THE ACTION POTENTIAL IN THEORY Depolarization of the cell during the action potential is caused by the influx of sodium ions across the membrane (去極化是鈉離子內(nèi)流造成的) Repolarization is caused by the efflux of potassium ions (復(fù)極化是鉀離子外流造成的)第51頁/共80頁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頁/共80頁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頁/共80頁55第54頁/共80頁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頁/共80頁Voltage clamp (電壓鉗) proves the above theory:第56頁/共80頁The Voltage-Gated Sodium Cha

52、nnel(電壓門控的鈉離子通道) The protein forms a pore in the membrane that is highly selective to Na+ ions (對Na+具有高度的選擇性). The pore is opened and closed by changes in the electrical potential of the membrane (Na+通道的開放和關(guān)閉具有電壓依從性).第57頁/共80頁Sodium channel structure(Na+ 通道的結(jié)構(gòu)) 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頁/共80頁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頁/共80頁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.電壓感受器第60頁/共80頁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頁/共80頁The patch-clamp (膜片鉗) Method- 40 mV65第62頁/共80頁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關(guān)閉開放失活去失活第63頁/共80頁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 (關(guān)閉) channel; 2. Opens (開放) 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關(guān)閉開放失活去失活第64頁/共80頁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頁/共80頁Putting the Piec