musclecell肌细胞-1(7年-2011年).ppt

,骨骼肌Skeletal Muscle,A single skeletal-muscle cell is known as a muscle fiber (肌纤维）. The nerve cells whose axons（轴突） innervate（支配） skeletal muscle fibers are known as motor neurons（运动神经元） 运动单位Motor Unit = a motor neuron + muscle fibers,神经肌接头的传递 Nuromuscular transmission,The alpha motoneuron branches, as it approches the muscle, sending axon terminals（轴突末梢） to several skeletal muscle fibers. Synaptic transmission（突触传递） occurs at the end-plate region （终板区）(i.e., the postsynaptic membranes 突触后膜) of the skeletal muscle fiber.,Ca 2+ 通道的开放和Ach 的释放,The axon terminal is enlarged into the terminal button. （末梢钮扣）Each terminal button contains thousands of vesicles that store Ach. Propagation of action potential the terminal triggers the opening of Ca 2+ channels in the terminal button. It permits Ca 2+ to diffuse into the terminal button from extracellular fluid, which in turn causes the release of Ach by exocytosis （出胞）from the vesicles.,终板电位 End plate potential,Binding of Ach with the receptor site in the motor end-plate induces the opening of channels ( both Na+ and K+，为化学门控通道). More Na+ moves inward than K+ outward, bringing about a depolarization of the motor end plate -This potential is known as end-plate potential (EPP). （终板膜本身无电压门控钠通道，故不会产生动作电位，但可形成局部电流） Local current can reach the threshold of adjacent muscle fiber membrane（邻近肌膜） and bring about an action potential.,乙酰胆碱酯酶Acetylcholinesterase,The surface of the motor end plate contains the enzymes acetylcholinesterase, which can break down（分解） free Ach in the cleft. As the concentration of free ACh falls because of its breakdown by acetylcholinesterase, less ACh is available to bind to the receptors. When receptors no longer contain bound Ach, the ion channels in the end plate close. The depolarized end plate returns to its resting potential and can respond to the subsequent arrival of ACh.,神经-肌接头传递各环节,Action potential in presynaptic nerve terminal depolarization Ca2+ channels open intracellular Ca2+ acetylcholine vesicle release ACh synaptic cleft binds to postsynaptic ACh receptor postsynaptic membrane depolarization end-plate potential (EPP) action potential in muscle cell occurs contraction of muscle cell.,箭毒传说,美洲的古印第安人在遇到敌人入侵时，女人和儿童在后方将箭毒木的汁液涂于箭头，供男人在战场上杀敌。1859年土著民族在和英军交战时，这种毒箭的杀伤力使英军惊恐万分。 传说西双版纳最早发现箭毒木汁液含有剧毒的是一位傣族猎人。这位猎人被一只硕大的狗熊紧逼而被迫爬上一棵大树，可狗熊仍不放过他,生死存亡的紧要关头，猎人折断一根树枝刺向正往树上爬的狗熊，奇迹突然发生了，狗熊立即落地而死。从那以后猎人就学会了把箭毒木的汁液涂于箭头用于狩猎。,又称见血封喉树,“七上八下九倒地”，意思就是说，如果谁中了箭毒木的毒，那么往高处只能走七步，往低处只能走八步，但无论如何，走到第九步，都会倒地毙命,箭毒木又名加独树、剪刀树等,高可达30米，多分布于赤道热带地区，国内则散见于广东、广西、海南、云南等省区。现为濒临灭绝的稀有树种，国家三级保护植物。,南美箭毒 Curare,The deadly South American arrowhead poison curare binds strongly to the ACh receptors, but it does not open their ion channels and is not destroyed by acetylcholinesterase. When a receptor is occupied by curare, ACh cannot bind to the receptor. Hence, there is no EPP in the motor end plate and no contraction. Since the skeletal muscles responsible for breathing（呼吸）, curare poisoning can lead to death by asphyxiation（窒息）.,肉毒杆菌毒素 Botulin and ACh,Botulin is an enzyme that breaks down a protein required for the binding and fusion of ACh vesecles with the presynaptic membrane. Hence, it can block the release of acetylcholine from nerve terminals in neuromuscular junction. This poisoning is one of the most potent poisons, which can cause flaccid paralysis （肌肉松驰性瘫痪）.,生物武器,它造价低，技术难度不大，隐秘性强，可以在任何地方研制和生产。 有资料显示，以1969年为例，当时每平方公里导致50%死亡率的成本分别为：传统武器2000美元；核武器，800美元；化学武器，600美元；生物武器，1美元。,肉毒杆菌毒素-“穷人的原子弹”,肉毒杆菌毒素是最流行的两大生物武器之一, 是一种廉价和高效的杀人武器，其死亡率高达60%至70%。受害者症状是头痛、肢体瘫痪，如不及时治疗将在2至10天内死去。这种毒素可以批量生产，并可通过皮肤吸收、肺部吸收、眼睛接触、等方式传染。,肉毒杆菌毒素-“富人的美容剂”,肉毒杆菌毒素除皱纹的原理很简单，A型肉毒毒素可以起到麻痹肌肉的作用，脸部注射后，阻断神经和肌肉之间的信息传导，可使局部肌肉瘫痪，肌肤因此舒展，皱纹便神奇般消失 A型肉毒毒素注射过量可致人死命。但美容除皱注射的A型肉毒毒素是人致死量的3%。注入肌肉后它选择性使肌肉松弛，几乎无多余的A型肉毒毒素进入血液或进入人脑脊液。,有机磷 Organophosphates and acetylcholinerase,Some organophosphates, which are the main ingredients in certain pesticides（农药）and “nerve gases”, inhibit acetylcholinesterase. When ACh binds to the end plate receptors, which is not destroyed, producing a maintained depolarization in the end plate and muscle plasma membrane. Hence, sodium channels enter an inactive state. Muscle does not contract in response to subsequent nerve stimulation, and result is death from asphyxiation（窒息）.,Organization of skeletal muscle,Skeletal muscle is made of individual muscle fibers（肌纤维）. The muscle fibers are made of fibrils（肌原纤维）. The fibrils are divided into individual filaments（肌丝）. The filaments are made up of the contractile proteins（收缩蛋白）.,肌丝 Filaments,The myofibrils （肌原纤维） contain thick （粗肌丝）and thin filaments（细肌丝） composed of contractile proteins. 粗肌丝Thick filaments contain the protein myosin （肌球蛋白，含有横桥）. Thin filaments contain proteins actin（肌动蛋白）, tropomyosin（原肌球蛋白）, and troponin（肌钙蛋白）.,横管 T Tubule 与肌浆网 SR 之间的关系,Transverse Tubule （T tubule 横管）is formed as an invagination （凹入）of the surface of the muscle membrane. The action potential spreading over the surface of the muscle membrane is propagated into the network of T tubules, which forms contacts with sarcoplasmic reticulum (SR肌浆网) SR contains a high concentration of Ca 2+,肌质网 SR and Ca2+ release,The T tubule membrane contains dihydropyridine receptor (二氢吡啶受体, a voltage-sensitive receptor 电压敏感受体，L-型Ca2+ 通道) When an action potential is propagated down the T tubule, the local depolarization activates dihydrpopyridine recepotor that in turn opens the Ca2+ release channel （终池上的钙离子释放通道, also known as ryanodine receptor ) on SR.,肌钙蛋白及其作用,由三个亚单位组成：肌钙蛋白T（TnT)、肌钙蛋白I(TnI)和肌钙蛋白C(TnC) TnT与原肌球蛋白结合，将整个肌钙蛋白固定在原肌球蛋白上。 TnC可与Ca+结合。 TnI的作用是TnC可与Ca+结合时，将信息传给原肌球蛋白，引起后者发生构象变化并向肌纤蛋白双螺旋沟深部滑行，从而暴露肌纤蛋白的结合位点，使横桥与之结合。,粗肌丝、横桥与细肌丝的关系,Pulling thin filaments inward by the bend of cross bridges is directed toward the center of the thick filament. Each thick filament is surrounded by six thin filaments, all the which are pulled inward simultaneously through cross-bridge cycling during muscle contraction.,从神经元动作电位到肌纤维收缩-(1),1. Action potential is initiated and propagates in motor neuron axon. 2. Action potential triggers release of Ach from axon terminals at neuromuscular junctions. 3. Ach binds to receptor sites on motor end plate in muscle fiber, opening Na+,K+ ion channel.,从神经元动作电位到肌纤维收缩-(2),4. More Na+ moves into the fiber at the motor end plate than K+ move out, depolarizing the membrane, producing the end-plate potential (EPP). 5. Local currents depolarize the adjacent plasma membrane to its threshold potential, generating an action potential that propagates over the muscle fiber surface and in to the fiber along T tubles.,从神经元动作电位到肌纤维收缩-(3),6. Action potential in T tubules triggers release of Ca2+ from lateral sacs of SR. 7. Ca2+ binds to troponin（肌钙蛋白） on thin filaments, causing tropomyosin（原肌球蛋白） to move away from its blocking position and thus uncovering cross-bridges binding sites on actin（肌纤蛋白）.,从神经元动作电位到肌纤维收缩-(4),8. Energized myosin cross-bridges （高能肌球蛋白横桥） on the thick filaments bind to actin（肌纤蛋白）.（横桥之所以处于高势能状态, 是因其头部具有ATP酶活, 并可将与其结合ATP分解成ADP和无机磷酸而贮能.） 9. Cross-bridge binding triggers release of energy stored in myosin（肌球蛋白）, producing a movement of each cross bridge. 此时ADP和无机磷酸便与横桥分离,10. 在ADT分离点， ATP binds to myosin（肌凝蛋白）, breaking linkage between actin（肌纤蛋白）and myosin and thereby allowing cross bridges to dissociate from actin.(横桥头部与ATP结合后，其对肌纤蛋白的亲和力降低，使其与纤动蛋白解离）。 11. ATP bound to myosin is split by myosin ATPase, transferring energy to myosin cross bridge once again.（结合到横桥头部的ATP被ATP酶分解，又把能量贮存在横桥）,从神经元动作电位到肌纤维收缩-(5),从神经元动作电位到肌纤维收缩-(6),12. Cross bridges repeat steps 8 to 11, producing movement of thin filaments past thick filaments. Cycles of cross-bridge movement continue as long as Ca2+ remains bound to troponin（肌钙蛋白）.,Relaxed state of the muscle,The normal concentration of Ca2+ in the cytosol that bathes the myofibrils（肌原纤维） is too little to elicit contraction. Therefore, in the resting state, the troponin -tropomyosin complex keeps the actin filaments inhibited and maintains a relaxed state of the muscle.,Function of ATP,1. Hydrolysis of ATP by myosin energizes the cross bridges, providing energy for force generation. 2. Dissociates cross bridges bound to actin. 3. Provides the energy for the active transport of Ca 2+ into lateral sacs of reticulum, lowering cytosolic Ca 2+.,肌肉收的形式和力学分析,Isometric contraction（等长收缩）: When a muscle develops tension but does not shorten. (长度不变, 张力增加) Isotonic contraction（等张收缩）: When a muscle is shortening but its tension remains constant. (长度缩短,张力不变),等张收缩举例 An example of isotonic contraction,手臂可以提起一个物体时的状态 Lifting an object: When the tension developing in your biceps becomes great enough to overcome the weight of the object in your hand, you can lift the object, with the whole muscle shortening. Because the weight of the object does not change as it is lifted, the muscle tension remains constant throughout the period of shortening. This is isotonic contraction.,等长收缩举例 An example of isometric contraction,想提起一重物, 但太重提不起时的状态 Try to lift an object: What happens if you try to lift an object too heavy for you , that is , if the tension you are capable of developing in your arm muscles is less than that required to lift the object ? The muscle cannot shorten and lift the object but remains at constant length in spite of the development of tension. This is an isometric contraction,前负荷 Preload and 后负荷 Afterload,前负荷: 肌肉在收缩前就加上肌肉上的负荷. The force required to stretch the muscle to lengths beyond 2.0 m). 后负荷: 肌肉开始收缩后遇到的负荷. The weight that a muscle lifts during an isotonic contraction).,最适长度 Optimal length,最适长度: The length at which the muscle fiber develops the greatest tension. At an initial sarcomere length（肌小节长度） of 2.2 um, each cross-bridge can bind to an actin molecule on thin filaments, and a maximum force is generated.,长度与张力的关系 Length-tension relationship,Maximal tetanic contraction can be achieved when a muscle fiber is at its optimal length. When it is longer, fewer thin-filament binding sites are accessible for binding with thick-filament cross bridges, because the thin filaments are pulled out. When the fiber is shorter, fewer thin-filament binding sites are exposed to thick-filament cross bridges because the thin filaments overlap.,体内长度与张力的关系 Length-tension relationshipin the body,In the body, the muscle relaxed length is approximately their optimal length, thus, the muscle are capable of achieving near-maximal tetanic contraction most of the time. Because of limitations imposed by attachment to the skeleton, a muscle cannot be stretched or shortened more than 30% of its resting optimal length, even at the outer limits (130% and 70% of optimal length), the muscle are still able to generate half their maximal tension.,负荷与速度的关系 Load-velocity relationship,The greater the load, the lower the velocity at which a single muscle fiber shortens during an isotonic contraction. The velocity of shortening is maximal when there is no external load . The velocity of shortening progressively decreases with an increasing load, and falls to zero when load cannot be overcome by maximal tension.,频率与张力的关系 Frequency and tension relation,潜伏期 Latent period: Following the action potential , there is a interval of a few milliseconds before the tension in muscle fiber begins to increase ( the processes associated with excitation -contraction coupling ) 单收缩 Single twitch: A mechanical response of a muscle fiber to a single action potential,频率与张力的关系 Frequency and tension relation,强直收缩Tetanus : A maintained contraction in response to repetitive stimulation. 不完全强直收缩Incomplete tetanus: At low stimulation frequencies, the tension may oscillate as the muscle fiber partially relaxes between stimuli. 完全强直收缩Complete tetanus: Produced at high frequency, with no oscillations.,强直收缩与横桥结合位点 Tetanus and cross-bridge binding sites,随着动作电位产生的频率增加，钙持续升高，最大数量的横桥结合位点都被打开，所以可达到最大的强直收缩. As frequency of action potential increases, the duration of elevated Ca2+ concentration increases and maximal number of cross-bridge binding sites remain uncovered, so that maximal tetanic contraction is reached.,生理条件下的骨骼肌收缩,在生理条件下, 支配骨骼肌的传出神经总是发出连续的神经冲动(动作电位), 所以骨骼肌的收缩几乎都是强直收缩. 骨骼肌弱收缩通常是由较小的运动单位motor unit) 产生, 而骨骼肌的强收缩是多由较大的运动单位产生. 骨骼肌强直收缩时,肌细胞连续兴奋,使胞浆内的Ca2+浓度持续上升, 可利用的横桥结合位点数目达到最大, 故收缩张力可达到一个相对稳定的最大值.,Types of smooth muscle,1. Single-unit smooth muscle: The whole muscle responds to stimulation as a single unit. This occurs because each muscle fiber is linked to adjacent fibers by gap junction. 2. Multiunit smooth muscle: Because these muscles have few gap junctions, each muscle fiber responds independently of its neighbors, and the muscle behaves as multiple units.,