生理学-细胞(双语).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,*,In order to understand the function of organs and tissues of the body,it is essential that we first study the basic physiological function of the cells,including,Transport across the cell membrane,Bioelectrical phenomena of the cell,Contraction of muscle,第 一 节 C膜的基本结构和物质转运功能,细胞膜的作用：,屏障作用,物质转运功能,跨膜信息传递功能,C膜的兴奋功能,一.膜的化学组成和分子结构,1.化学组成：,三种,1）脂类,：,多,特点：,熔点低，常温下呈液态,磷酸+碱基,脂肪酸长烃链,（,*,熔点、胆固醇含量决定C膜的流动性）,2.膜的分子结构：,其基本内容是：,1）基架：液态脂质双分子层,2）中间：镶嵌有不同分子结构和功能的蛋白质，其以-螺旋或球形结构形式存在。,3）外表面：,糖脂或糖蛋白,液态镶嵌模型,表面蛋白质,疏水性基团,亲水性基团,（磷酸+碱基）,细胞外,结合蛋白质,糖蛋白 糖脂,细胞内,（,脂肪酸长烃链）,液态镶嵌模型,二.,C膜物质转运功能,*,跨膜转运的方式：,单纯扩散,易化扩散,主动转运,出胞和入胞,.单纯扩散,（simple diffusion）,扩散的原理：布郎运动（图示）,扩散,：,指溶质分子由高浓度处向低浓度处的运动,扩散通量：,molcm,2,s,决定因素：,与该物质的浓度差成正比，与其他溶质无关,1.,*,概念：,脂溶性,物质由C膜,高,浓度一侧向,低,浓度一侧的转运过程（如：O,2,，CO,2,）。,2.决定因素：,1）膜两侧该物质浓度差,2）膜对该物质的通透性,.易化扩散,Facilitated Diffusion,1.,*,概念：,非,脂溶性物质在膜,蛋白质,的协助下，由膜,高,浓度一侧向,低浓度一侧的扩散。,2.特点：,1）顺浓度差转运,2）选择性转运,（膜蛋白质结构）,3）受膜两侧因素改,变的调控,3.类 型：,两种,1,）通道介导的,Facilitated diffusion through channel,由,离子通道,完成,（指与离子转运有关的,膜蛋白）,转运带电离子,(,Na,+、,K,+、,Ca,2+,),依靠通道的易化扩散,转运的物质:各种带电离子,通 道,阻 断 剂,Na,+,河豚毒,(TTX）,Ca,2+,Mn,2+,、维拉帕米,K,+,四乙基铵,通道特点：,（1）,相对特异性,（2）,通道状态的变化：,三种,激活状态（开）：,离子扩散,失活状态（关）：,刺激不能开放,备用状态 （关）：,刺激能开放,化学门控通道化学物质,（Ach）,电压门控通道膜两侧电位差,机械门控通道机械刺激,通道类型：,三种,通道的功能意义：,通过转运离子，,完成跨膜信号传递,Facilitated diffusion through channel:Voltage-gated ion channel,Chemically-gated ion channel,Mechanically-gated ion channel,通道开放,离子进入膜内,神经递质,（Ach）,离子,细胞外,细胞内,Some transport proteins have watery spaces all the way through the molecule and allow free movement of certain ions or molecules.They are called,channel proteins.,Diffusion carried out by protein channel is termed channel mediated diffusion.,2）载体介导的,Facilitated diffusion via carrier,特点：,高度特异性,substrate,flux,载体,扩散,竞争性抑制,饱合现象,意义:,转运代谢物质,（葡萄糖、氨基酸由膜载体蛋白完成,载体中介的易化扩散,细胞膜,细胞外,细胞内,载体蛋白,载体蛋白,细胞内,细胞外,氨基酸,载体蛋白质,氨基酸,载体介导的,依靠载体的易化扩散,转运的物质：葡萄糖、氨基酸等小分子亲水物质,Concept:Diffusion carried out by carrier protein,Substance:glucose,amino acid,Mechanism:a“ferry”or“shuttle”process,Facilitated Diffusion via carrier,Facilitated Diffusion,Definition:Facilitated diffusion means the diffusion of lipid insoluble or water soluble substance across the membrane down their concentration gradients by aid of membrane proteins(carrier or channel),Substances:K+,Na+,Ca2+,glucose,amino acid,urea etc.,.主动转运,Active transport,1.,*,概念:,细胞通过本身某种,耗能,过程,将某物质从膜,低,浓度一侧转运到,高,浓度一侧的过程。,2.原发性主动转运：,钠钾泵,（,*,钠泵）,1)钠泵的本质:钠钾依赖式ATP酶,2）作用:,分解ATP供能，逆浓度差转运,Na,+,、K,+,（泵入,K,+,、泵出Na,+,）,离子通道转运与钠-钾泵转运模式图,泵,3Na,+,2K,+,ATP,ADP,细胞,3）钠泵活动的意义,（能量的2030%）,（1）形成和保持C内外Na,+,、K,+,的不均衡分布,K,+,i,K,+,o,30倍,Na,+,o,Na,+,i,10倍,（2）建立势能贮备，以,供给细胞的其它耗能过程来利用。,（代谢反应、水平衡、膜电位）,细胞外,细胞内,2K,+,2K,+,3Na,+,3Na,+,钠泵,ATP催化部位Na,+,浓差,K,+,浓差,钠钾泵转运：,3.继发性（联合转运）,1）特点：,间接耗能（钠泵势能储备）,与膜中特殊蛋白质有关,2）类型：,同向转运,逆向转运,4.主动转运特点：,1）逆浓度差；2）耗能,泵,Na,+,K,+,ATP,ADP,Na,+,Na,+,继发性主动转运,细胞,G,H,+,H,+,细胞外,细胞内,K,+,K,+,钠泵,Na,+,Na,+,低浓度,Na,+,高浓度,Na,+,转运体,高浓度,G,低浓度,G,联合转运：,Active transport,When the cell membrane moves molecules or ions,uphill,against a concentration gradient(or uphill against an electrical or pressure gradient),the process is called active transport,Primary active transport,:,the energy used to cause the transport is derived,directly,from the breakdown of ATP or some other high-energy phosphate compound,Secondary active transport:,The energy is derived,secondarily,from energy that has been stored in the form of ionic concentration differences between the two sides of the membrane,created in the first place by primarily active transport,Categories of Transport Across the Plasma Membrane,Cell membrane is selectively permeable to some molecules and ions.,Mechanisms to transport molecules and ions through the cell membrane:,Non-carrier mediated transport.,Simple Diffusion.,Facilitated Diffusion:,Via Carrier and Channel.,Voltage,Chemical and Mechanical gating channel,Active Transport,May also be categorized by their energy requirements:,Passive transport:,Net movement down a concentration gradient,does not need ATP,Active transport:,Net movement against a concentration gradient,needs ATP,.,出胞与入胞,1.概念,指大分子或固态、液态物质团块，通过膜的结构和功能变化,出、入,C的过程。,2.出胞,1）C,的分泌活动,2）神经递质的释放,3.入胞：,物质团块（细菌、病毒等）入胞,（吞噬、吞饮）,出胞示意图,入胞示意图,Ca,2+,Ca,2+,入胞,出胞,再循环囊泡,次级溶酶体,吞饮小泡,胞内体,H,+,被动与主动转运方式的比较：,被动转运,主动转运,单纯扩散 易化扩散,通道 载体,原发性 继发性,转运方向,高浓度低浓度,低浓度高浓度,膜转运蛋白,否,需,需,需,需,饱和现象,无,有,无,有,有,化学特异性,无,有,有,有,有,消耗代谢能,及来源,不消耗,消耗,钠泵,消耗,离子浓差,钠泵,转运的物质,O,2,CO,2,脂肪酸,Na,+,K,+,Ca,+,葡萄糖,氨基酸,Na,+,、K,+,Ca,+,、H,+,葡萄糖,氨基酸,第 三 节,细胞的跨膜电变化,一.兴奋性,（excitability）,活的组织或C对剌激发生反应,（产生动作电位-近代）,的能力,2.,*,兴奋（excitation）,C受刺激时产生反应(,动作电位,)的过程,概 念,1.,*,兴奋性,生理功能改变,环境变化,机体,(刺激),（反应）,1.概念,：,机体所处的内、外环境变化,2.类型,时间,强度,1）刺激强度,2）刺激持续时间,3）强度-时间变化率,3.刺激的三要素,.刺 激,Stimulus,概念,引起组织产生反应（,动作电位,）所需的最小刺激强度,(阈上刺激、阈下刺激),意义,是衡量组织兴奋性高低的指标,阈值,1,*,阈强度,（阈值）,Threshold,(intensity):,兴奋性,1.概念,机体受刺激时其功能活动的改变,2.形式,1)兴奋静止 活动,或,活动弱 强,2)抑制：活动 静止,或,活动强 弱,.反 应,.可兴奋细胞（组织）,刺激能产生动作电位的C（组织）,(神经、肌肉、腺体),二.C 的生物电现象,.静息电位,（Resting Potential,RP,）,*,1.概念,静息时，存在于C膜内外的电位差,安静时 静息电位,受刺激时 动作电位,表现形式：,2.特点：,1）膜内膜外,2）为稳定的直流电,R,0 mV,-70-90mV,神经纤维,RP,静息电位,的测量实验,4.,*,RP形成原理：,由,K,+,离子外流形成，相当于,K,+,平衡电位（,E,K,）。,1）K,+,外流,条件,静息时，C膜对,K,+,的通透性高K,+,通道开放）,2）K,+,外流,动力,C内外离子分布不均：,K,+,i,K,+,o,30倍,3.RP的数值,30KCl,1KCl,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,半透膜,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,假设,1,：半透膜对,K,和,Cl,-,都无通透性,.,假设2：半透膜对K,和Cl,-,都有,通透性,假设,3,：半透膜,只对,K,有通透性,30KCl,半透膜,1KCl,+,+,+,+,+,+,-,-,-,-,-,-,电势能,浓差势能,+,K,+,K,+,K,+,外流形成,K,+,平衡电位,神经纤维,电势能,30K,+,1 K,+,+,+,+,+,+,+,+,+,+,+,P,-,浓差势能,E,K,=59.5 log,K,+,平衡电位,可由,Nernst,公式计算,5.决定,RP,的因素,RP实测值略,计算值。,K,+,o,K,+,i,（mV）,why？,1,）跨膜,K,+,浓差：,2）,膜对,K,+,的通透性,K,+,o,RP,RP,Concept of Resting Potential(RP),A potential difference across the cell membrane at the rest stage or when the cell is not stimulated.,Property:,*It is constant or stable,*It is negative inside relative to the outside,*Resting potentials are different in different cells.,Conclusion.,The formation of resting potential depends on:,Concentration difference of K,across the membrane,Permeability of Na,+,and K,+,during the resting state,Na,+,-K,+,pump,*,电生理学名词：,+,神经纤维,+,+,+,+,+,+,+,+,+,+,RP:-90mV,-100mV,-50mV,1.极 化,Rp时，膜两侧保持的内负外正状态,2.除（去）极化,膜内电位（RP值）向负值减小的方向变化,3.复极化,膜去极后，向膜内负电位,（RP）,恢复的过程,4.超极化,膜内电位（,Rp值,）向负值加大的方向变化,Basic Electrophysiological Terms I:,Polarization,:a state in which membrane is polarized at rest,negative inside and positive outside.,Depolarization,:It means the membrane potential becomes less negative than the resting potential(close to zero).,Hyperpolarization,:It means that the membrane potential is more negative than the resting level.,Reverspolarization,:It refers as a reversal of membrane potential polarity.The inside of a cell becomes positive relative to the outside.,Repolarization,:It means restoration of normal polarization state of membrane.It is a process in which the membrane potential returns toward from depolarized level to the normal resting membrane value.,.,动作电位,(Action Potential,AP),stimulatr,0mV,神经纤维,AP,C兴奋的共有标志,指C受刺激时，在RP基础上，膜电位产生的快速倒转和复原,2.AP的波形及组成,1)锋电位,2)后电位,负后电位（去极化）,正后电位（超极化）,1.*AP的概念,时间（ms）,正后电位,负后电位,-70,-55,0,+35,mV,刺激伪迹,锋电位,动作电位的波形及组成,后电位,时间（ms）,-70,-55,0,+35,mV,动作电位的波形及组成,去极相,复极相,静息期,超射,2）复极相：,K外流形成（,Na,+,通道关闭）,3）静息期:,Na,+,泵活动,Na,+,、K,+,交换,3.Ap产生的机制,泵出Na,+,泵入 K,+,1）去极相：,Na,+,通道开放，Na,+,快速内流形成。,超射值,相当于Na,+,平衡电位,（,E,Na,）,细胞膜电压门控性Na,+,通道激活开放，Na,+,内流,-,-,-,-,-,-,-,-,+,Na,+,Na,+,+,+,+,+,+,+,-,-,-,-,-,+,+,+,+,+,+,细,胞,外,细,胞,内,1NaCl,Na,+,浓度差,12 NaCl,RP,刺激,AP产生的机制：,1）去极相,RP,K,+,K,+,细胞外,1NaCl,12 NaCl,-,+,细胞内,Na,+,K,+,-,+,泵,3）静息期,2）复极相,4.,*,AP的特征,：,全或无现象(All or None),AP,刺激,R,S,指同一C上，AP的大小不随剌激强度和传导距离而改变的现象,5.,*,决定AP幅度的因素,1）,Na,+,o,2）Na,+,通道状态,细胞受到刺激时,细胞膜上,少量Na,+,通道激活而开放,Na,+,顺浓度差少量内流膜内外电位差,局部电位,当膜内电位变化到阈电位时,Na,通道大量开放,膜内负电位减小到零并变为正电位（,AP上升支,）,Na,+,通道关Na,+,内流停+同时,K,+,通道激活而开放,K,顺浓度差和膜内正电位的吸引,K,迅速外流,膜内电位迅速下降，恢复到RP水平（,AP下降支,）,Na,+,i,、,K,+,O,激活Na,+,K,+,泵,Na,+,泵出、K,+,泵回，离子恢复到兴奋前水平,后电位,AP的产生机制,Concept,Action potential is a rapid,reversible,and conductive change of the membrane potential after the cell is stimulated.,Nerve signals are transmitted by action potentials.,Action Potential Summary,Reduction in membrane potential (depolarization)to threshold level leads to opening of Na,+,channels,allowing Na,+,to enter the cell,Interior becomes positive,The Na,+,channels then close automatically followed by a period of inactivation.,Next K,+,channels open,K,+,leaves the cell and the interior again becomes negative.,Process lasts about 1/1000th of a second.,Basic Electrophysiological Terms II:,Excitability,:The ability of the cell to generate the action potential,Excitable cells,:Cells that generate action potential during excitation.So in excitable cells(muscle,nerve,secretery cells),the action potential is the,marker,of excitation.,Some scholars even suggest that in excitable cells,action potential is identical to the excitation.,Stimulus,:It is a sudden change of the(internal or external)environmental condition of the cell.It includes physical and chemical stimulus.The electrical stimulus is often used for the physiological research.,Threshold,(intensity):the lowest or minimal intensity of stimulus to elicit an action potential,(Three factors of the stimulation:intensity,duration,rate of intensity change),Types of stimulus:,Threshold stimulus,:The stimulus with the intensity equal to threshold,Subthreshold stimulus,:The stimulus with the intensity weaker than the threshold,Suprathreshold stimulus,:The stimulus with the intensity greater than the threshold.,0,mV,-70,-90,20,绝对不应期,相对不应期,超常期,0,100,兴奋性,低常期,.组织,兴奋后,其,兴奋性周期性的变化,分 期 兴 奋 性 原 因 时 间,绝对不应期 钠通道均失活,0 -60 mV,相对不应期 正常 少数钠通道复活,-60-80 mV,超常期 正常 多数钠通道复活,-80-90 mV,低常期 正常 超极化,-90 mV,1.兴奋性变化分期：,2.绝对不应期的意义：,其长短决定细胞兴奋的最高频率,例：绝对不应期 2 ms,兴奋的最高频率?,1000/2=500 Hz,使Ap不会重合,-70,-55,-85,膜电位,（mV）,记录,刺激,AP,阈电位水平,局部兴奋,Rp水平,刺激,三.AP的引起和在同一C的传导,阈电位和锋电位的引起,*,阈电位,(threshold potential）,1.概念,能诱发,AP,（,钠通道大量激活,）的临界膜电位值,2.,数值：,比RP的绝对值小 10 20 mV,3.意义：,是,AP,产生的条件,局部兴奋,Local Response,及其特性,1.概 念,阈下刺激引起,膜局部,电位的较小去极化,2.产生机制,少量Na,+,内流形成,3.特 点,1)不是“全或无”的,时间,空间,2)呈电紧张性扩布,3)可以叠加（总和）,Experiments:,-90,-70,-110,-90,-70,-110,R,S,阈下刺激,电紧张扩布,空间,时间,局部兴奋与AP的区别:,不衰减扩布,电紧张扩布,传播特点,无,有,总和现象,有,无,全或无特点,大,小,膜电位变化幅度,多,少,钠通道开放数,阈或阈上刺激,阈下刺激,刺激强度,AP,局部兴奋,区别,Threshold Potential,Threshold potential,plays a key role in the genesis of action potential.,Threshold potential,is a critical membrane potential level at which an action potential can occur.,Why can all the Na+channel open at the threshold potential?It is dependent on the gating property of the voltage-gated Na+channels.,The value of threshold potential of most excitable cell membrane is about 15 to 20 mV less negative than the resting potential.,The,threshold stimulus,is just strong enough to depolarize the membrane to the threshold potential level,therefore it can cause an action potential.,1.传导机制局部电流,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,+,-,-,+,-,+,-,+,.兴奋在同一细胞的传导,Propagation of the Action Potential,神经冲动：,神经纤维上传导着的Ap,神经纤维,静息部位膜内为负电位，膜外为正电位,兴奋部位膜内为正电位，膜外为负电位,在兴奋部位和静息部位之间存在着电位差,膜外的正电荷由静息部位向兴奋部位移动,膜内的负电荷由兴奋部位向静息部位移动,形成局部电流,膜内：兴奋部位相邻的静息部位的电位上升,膜外：兴奋部位相邻的静息部位的电位下降,去极化达到阈电位，触发邻近静息部位膜爆发新的AP,局部电流,传导机制：,局部电流 local current flow,有髓鞘神经纤维为远距离(跳跃式)局部电流,第 四 节,肌细胞的收缩功能,Muscle Contraction,一.骨骼肌C的收缩机制,（一）.骨骼肌C的微细结构,1.肌原纤维和肌小节,肌纤维膜,肌细胞核,终末池,肌原纤维,线粒体,三联管,T小管,肌质网,细胞液,肌小节,（肌肉收缩、舒张的最基本单位）,2.肌管系统,1）横管系统,（T管）,将兴奋传向肌C深部,2）纵管系统,（肌质网、L管）,储存、释放、再积聚钙,3）三联管,连接兴奋收缩的关键部位,肌管系统,（二）骨骼肌的兴奋收缩偶联,Excitation/contraction coupling,1.概念,把肌纤维兴奋和收缩连接起来的中介过程,.基本过程,Ap沿,T,管传向肌C内部,三联管处的信息传递,肌浆网释放与再聚积Ca,2+,3.关键部位:,三联管,耦联因子:,Ca,2+,（三）.骨骼肌收缩的分子机制,1.主要内容,细肌丝向粗肌丝之间滑行肌小节缩短,2.肌丝的分子组成,滑行学说,Changes in the appearance of a Sarcomere during the Contraction of a Skeletal Muscle Fiber,肌凝蛋白(Myosin）组成,（,收缩蛋白质,）,*,横桥的特性：,具有ATP酶活性，供能与细肌丝可逆结合、向线摆动,粗肌丝：,长杆状主干,球状部横桥,原肌凝蛋白,（,tropomyosin）,肌纤蛋白,（actin）,肌钙蛋白,（troponin）,细肌丝:,肌纤蛋白,（,actin）,原肌凝蛋白,（,tropomyosin）,肌钙蛋白,（,troponin）,（收缩蛋白质）,调节蛋白质,肌节缩短=肌细胞收缩,牵拉细肌丝朝肌节中央滑行,横桥摆动,横桥与结合位点结合，,分解ATP释放能量,原肌球蛋白位移，,暴露细肌丝上的结合位点,Ca,2,+,与肌钙蛋白结合,肌钙蛋白的构型,终池膜上的钙通道开放,终池内的Ca,2,+,进入肌浆,3.,肌丝滑行过程,肌膜AP沿横管膜传至三联管,终池膜上的钙通道开放,终池内Ca,2+,进入肌浆,Ca,2+,与肌钙蛋白结合,引起肌钙蛋白的构型改变,原肌凝蛋白发生位移,暴露出细肌丝上与横桥结合位点,横桥与结合位点结合,激活ATP酶作用,分解ATP,横桥摆动,牵拉细肌丝朝肌节中央滑行,肌节缩短=肌细胞收缩,小结：骨骼肌收缩全过程,舒张过程：,细肌丝滑出,Ca,2+,与,TnC,解离,Ca,2+,泵将Ca,2+,泵入终末池,Ca,2+,i,肌纤蛋白,与横桥分离,肌肉舒张,Excitation-Contraction Coupling,Depolarization of motor end plate(excitation)is coupled to muscular contraction,Nerve impulse travels along,sarcolemma,and down T-tubules to cause a release of Ca,2+,from SR,Ca,2+,binds to,troponin,and causes position change in,tropomyosin,exposing active sites on,actin,Permits strong binding state between,actin,and myosin and contraction occurs,ATP is hydrolyzed and energy goes to myosin head which releases from,actin,二.骨骼肌收缩的外部表现与力学分析,1.前负荷（Preload）,2.后负荷(afterload),外部表现,产生缩短,产生张力,肌肉收缩,遇到,的负荷,骨骼肌收缩的形式,2）意义：维持人体的位置和姿势,1.等长收缩,(isometric contraction),1）,*,概念,肌肉收缩时，长度不变而张力增加,2.等张收缩,(isotonic contraction),1),*,概念,肌肉收缩时，张力不变而长度缩短,2)意义：作功,3.单收缩与单收缩的复合,1)单收缩（,single twitch,）,肌肉受到一次刺激引起的一次收缩和舒张,2)单收缩的复合（强直收缩,Tetanus,）,(1)概念,连续多个刺激引起肌肉的持续性收缩,(2),类型,不完全强直收缩,（,incomplete tetanus,）,完全强直收缩,（,complete tetanus,）,单收缩与强直收缩,单收缩,不完全强直收缩,完全强直收缩,Twitch,:a brief mechanical contraction of a single fiber produced by a single action potential at low frequency stimulation is known as single twitch.,Tetanus,:It means a summation of twitches that occurs at high frequency stimulation,*,影响骨骼肌收缩的主要因素,Factors that Affect the Efficiency of Muscle Contraction,2）影响,在一定范围内前负荷肌张力,最适前负荷,（最适初长度）,指产生最佳收缩效果的前负荷,最适前负荷,肌张力,.前负荷,Preload,（初长度,Initial length,）,1）,*,概念：,肌肉收缩前就遇到的负荷,.后负荷,（,Afterload）,前负荷不变,后负荷,（最大张力）,产生的张力,缩短延迟,缩短速度,收缩的阻力或作功对象,2）,影 响,1）*,概念,肌肉收缩开始时遇到的负荷,.肌肉收缩能力,1),*,概念,指影响收缩效果的肌肉内部功能状态,2)影响肌肉收缩能力的因素,降低,缺氧、酸中毒,能源物质,加强,钙离子、咖啡因,肾上腺素,