神经电生理数学模型-Hodgkin-Huxley方程课件.ppt
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1、n 应用数学方法建立神经元膜上动作电位产生和在传导的模型应用数学方法建立神经元膜上动作电位产生和在传导的模型。n Hodgkin and Huxley Model was published in 1952 described a series of experiments that allowed the development of a model of the action potential. n This work was awarded a Nobel Prize in 1963.n Partial Differential Equation (PDE): function of
2、time and length Ordinary Differential Equation (ODE): function of timen Neural system is consisted of millions of neurons(1012), neuron is the basic unit of the neural system. 前言前言BackgroundGiant axon of squid 9.1 9.1 动作电位产生和传导的神经生物学机制动作电位产生和传导的神经生物学机制9.1.1 神经细胞与神经信息传递神经细胞与神经信息传递9.1.2 神经细胞膜的离子通道特性神经
3、细胞膜的离子通道特性9.1.3 动作电位与神经细胞膜离子通道特性动作电位与神经细胞膜离子通道特性9.1.1 神经细胞与神经信息传递神经细胞与神经信息传递nsoma 胞体胞体nsynapse 突触突触ndendrite 树突树突nAxon 轴突轴突Diagram of typical neuron神经细胞神经细胞神经细胞各个部分在信息传递中的作用神经细胞各个部分在信息传递中的作用nThe neurons cell body is connected to a number of branches The neurons cell body is connected to a number of
4、branches called dendritescalled dendrites(树突)(树突)and long tube called the axonand long tube called the axon(轴突)轴突)that connects the cell body to the presynapticthat connects the cell body to the presynaptic terminals (synapse terminals (synapse 突触突触). ). nDendrites are the receptive surfaces of the
5、neuron that receive Dendrites are the receptive surfaces of the neuron that receive signals from thousands of other neurons; signals from thousands of other neurons; nThe single axon is served as an transmission line to move The single axon is served as an transmission line to move information from
6、one neuron to anothersinformation from one neuron to anothers. . 9.1.2 神经细胞膜的离子通道特性神经细胞膜的离子通道特性 细胞膜把细胞内外分隔,细胞膜两侧的离子成分和浓度不同:细胞膜把细胞内外分隔,细胞膜两侧的离子成分和浓度不同: 细胞内细胞内 正离子:主要是钾离子正离子:主要是钾离子 负离子:有机小分子负离子:有机小分子 细胞外细胞外 正离子:主要是钠离子正离子:主要是钠离子 负离子:氯离子负离子:氯离子 在这两种方向相反的作用下达到平衡在这两种方向相反的作用下达到平衡时,没有离子通过细胞膜;时,没有离子通过细胞膜; 达到
7、平衡状态时,细胞膜内外的电位差称为该类离子的达到平衡状态时,细胞膜内外的电位差称为该类离子的Nernst电位电位V*; 不同类离子的不同类离子的Nernst电位不同。电位不同。神经细胞膜电活动神经细胞膜电活动由于细胞内外离子的浓度差,由于细胞内外离子的浓度差,某一种离子要从高浓度侧向低某一种离子要从高浓度侧向低浓度侧扩散。浓度侧扩散。由于离子带电,扩散到另一侧的由于离子带电,扩散到另一侧的离子积累起来的电荷排斥将扩散离子积累起来的电荷排斥将扩散过来的带有同一类电荷的离子。过来的带有同一类电荷的离子。平衡平衡离子通过离子通道的驱动力离子通过离子通道的驱动力设:细胞的膜电位为设:细胞的膜电位为V,
8、 某个离子的某个离子的Nernst电位为电位为V*;那么那么 (VV*)是这种离子通过该离子通道的驱动力。是这种离子通过该离子通道的驱动力。e.g. (VVNa)是钠离子通过细胞膜钠离子通道的驱动力。是钠离子通过细胞膜钠离子通道的驱动力。(VVk) 是钾离子通过细胞膜钾离子通道的驱动力。是钾离子通过细胞膜钾离子通道的驱动力。Neurons, like all living cells, are surrounded(包围)(包围) by a plasma membrane that is impermeable (不可渗透(不可渗透 )to ions. This property allows
9、 a neuron to maintain different concentrations of ions between the inside and outside of the cell.神经细胞膜内外不同的离子浓度神经细胞膜内外不同的离子浓度In a typical mammalian neuron, there is a large difference in the concentration of ions, such as sodium (Na+) and potassium (K+), between the intracellular and the extracellu
10、lar environments. In addition, the interior of the neuron has a high concentration of large negatively charged proteins.神经细胞膜内外不同的钾离子浓度、钠离子浓度神经细胞膜内外不同的钾离子浓度、钠离子浓度The plasma membrane is composed of a lipid bilayer (脂脂类类层层 ). Its hydrophobic (疏水)(疏水)nature prevents the diffusion of ions across the mem
11、brane.神经细胞膜神经细胞膜的构成和离子跨膜扩散的构成和离子跨膜扩散The only way ions can move across the lipid bilayer is by passing through specialized channels. These channels are transmembrane pores that permit the movement of particular ions while excluding others. Such channels can be in an open or closed state.神经细胞膜上不同类的离子通
12、道神经细胞膜上不同类的离子通道When a neuron is at rest, most ion channels are closed. However, some potassium channels (blue) are open, permitting potassium ions to diffuse out of the cell down their concentration gradient. Note that sodium channels are normally closed, and thus sodium ions cannot cross the membra
13、ne when the neuron is at rest.神经细胞膜静息:大部分通道关闭部分钾离子通道开启神经细胞膜静息:大部分通道关闭部分钾离子通道开启In a typical neuron, the internal concentration of potassium is higher than the external concentration. K+ ions are pulled by two opposing forces: First, a DIFFUSION FORCE drives K+ ions along their concentration gradient
14、towards the exterior of the cell.钾离子浓度细胞内高于细胞外钾离子浓度细胞内高于细胞外, , K K+ + ions ions 受扩散力推向细胞外受扩散力推向细胞外The movement of potassium ions out of the cell increases the internal negative charge. The positively charged potassium ions are attracted to the internal negative charge, and this ELECTRICAL FORCE pull
15、s potassium ions back into the cell.钾离子钾离子受受电相斥力推回细胞内电相斥力推回细胞内The diffusion and electrical forces eventually come into balance, and an electrical potential, or voltage, is reached at which the electrical force exactly balances the diffusion force. At this point, there is no NET movement of potassium
16、 ions into or out of the cell.两类相反的作用力达到平衡两类相反的作用力达到平衡, , 此时没有离子通过细胞膜此时没有离子通过细胞膜The electrical potential across the membrane can be measured by inserting an electrode into the cell. A neuron at rest has a voltage difference of about -70 -60 mv across the membrane.神经元的静息膜电压神经元的静息膜电压n 离子通道是分布在细胞膜上的跨膜蛋
17、白。离子通道是分布在细胞膜上的跨膜蛋白。 Ion channels are membrane protein complexes . They play an essential role in the diffusion of ions across cell membrane.n 具有复杂的门控(开关)特性,离子电导性决定神经元放电模式具有复杂的门控(开关)特性,离子电导性决定神经元放电模式 。 Gating: The conformational change between open and closed . open the conformation in which channel
18、 allow ions to pass; closed the conformation in which channel forbid ions to pass.n 离子通道的状态(关闭、开放和失活)与膜电位和时间有关,离子通道的状态(关闭、开放和失活)与膜电位和时间有关,n 某一个离子通道的状态可以通过测定通道的电导来评估。某一个离子通道的状态可以通过测定通道的电导来评估。Electrical properties of ion channels Ion channels can be classified according to their gating mechanism1. 电压门
19、控电压门控2. 配体门控配体门控细胞外配体细胞外配体 细胞内配体细胞内配体3. 机械门控机械门控根据门控机制的不同,离子通道可分为三类:根据门控机制的不同,离子通道可分为三类: 9.1.3 细胞膜离子通道特性与动作电位细胞膜离子通道特性与动作电位Action potentialn动作电位是神经元编码信息,及与其它神经元通讯的手段,动作电位是神经元编码信息,及与其它神经元通讯的手段,n动作电位的产生是由于神经细胞膜跨膜电位的变化,动作电位的产生是由于神经细胞膜跨膜电位的变化,n细胞膜上的钾离子通道、钠离子通道等离子通道电导特性,细胞膜上的钾离子通道、钠离子通道等离子通道电导特性, 在动作电位的产
20、生中起关键作用。在动作电位的产生中起关键作用。nH-H模型描述神经细胞膜上的离子通道电导状态产生和模型描述神经细胞膜上的离子通道电导状态产生和 沿着轴突传导动作电位。沿着轴突传导动作电位。nAction Potential: all-or-none: action potential does not decrease in amplitude as it is conducted away from its site of initiation;The action potential is due to voltage and time-dependent changes in condu
21、ctance.nResting potential: -70 -60mVnAction potential: +20 +30mVAction potential动作电位的动作电位的5个相位个相位n 静息电位(静息电位( The resting potential ):极化):极化(polarization)n 阈值电位(阈值电位(threshold)n 上升(上升(The rising phase):去极化():去极化(depolarization)n 下降(下降(The falling phase):复极化(:复极化(repolarization)n 恢复期(恢复期(The recovery
22、 phase)When the neuron is at rest, only a small subset of potassium channels are open, permitting K+ ions to enter and exit the cell based on electrochemical forces. For each K+ ion that leaves the cell, another returns, maintaining the membrane potential at a constant value.openclosedThe resting po
23、tential静息状态(极化)静息状态(极化)处于静息电位处于静息电位(-70 -70 60mV60mV)As a depolarizing stimulus arrives at the segment of the membrane, a few Na+ channels open, permitting Na+ ions to enter the neuron. The increase in positive ions inside the cell depolarizes the membrane potential (making it less negative), and br
24、ings it closer to the threshold at which an action potential is generated.Threshold阈值电位阈值电位当细胞膜受到刺激,部分Na+通道打开,允许Na+进入膜内。由于Na+离子内流,细胞膜内电位上升并超过阈值电位。If the depolarization reaches the threshold potential, additional voltage gated sodium channels open. As positive Na+ ions rush into the cell, the voltage
25、 across the membrane rapidly reverses and reaches its most positive value.openThe rising phase膜电位超过阈值电位,导致更多钠离子通道开放,电导GNa 增加,使钠离子内流;内流的钠离子电流导致进一步的去极化,使钠离子电流进一步增加。At the peak of the action potential, two processes occur simultaneously. First many of the voltage-gated sodium channels begin to close. S
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