骨骼肌医学知识讲座专家讲座.pptx

,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,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,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,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,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,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,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,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,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,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,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,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,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,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,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,单击此处编辑母版标题样式,Skeletal Muscle,骨骼肌,Qiang XIA(,夏强,),PhD,Department of Physiology,Room C518,Block C,Research Building,School of Medicine,Tel:[phone],Email:xiaqiang,骨骼肌医学知识讲座,第1页,Types of muscle:,Skeletal muscle,骨骼肌,Cardiac muscle,心肌,Smooth muscle,平滑肌,Striated muscle,横纹肌,Muscle,骨骼肌医学知识讲座,第2页,骨骼肌医学知识讲座,第3页,Muscle(cont.),The sliding filament mechanism,（肌丝滑行机制）,in which myosin,（肌凝蛋白）,filaments bind to and move actin,（肌纤蛋白）,filaments,is the basis for shortening of stimulated skeletal,smooth,and cardiac muscles.,In all three types of muscle,myosin and actin interactions are regulated by the availability of calcium ions.,Changes in the membrane potential of muscles are linked to internal changes in calcium release(and contraction).,骨骼肌医学知识讲座,第4页,Neuronal influences on the contraction of muscles is affected when neural activity causes changes in themembrane potential of muscles.,Smooth muscles operate in a wide variety of involuntaryfunctions such as regulation of blood pressure andmovement of materials in the gut.,Muscle(cont.),骨骼肌医学知识讲座,第5页,Structure of skeletal muscle,骨骼肌医学知识讲座,第6页,Skeletal muscles,are attached to the,skeleton by tendons.,Skeletal muscles typically contain,many,many muscle fibers.,骨骼肌医学知识讲座,第7页,The sarcomere,（肌小节）,is composed of:,thick filaments called myosin,anchored,in place by,titin fibers,and,thin filaments called actin,anchored to,Z-lines,.,骨骼肌医学知识讲座,第8页,A cross section through a sarcomere shows that:,each myosin can interact with 6 actin filaments,and,each actin can interact with 3 myosin filaments.,骨骼肌医学知识讲座,第9页,Sarcomere structures in an electron micrograph.,骨骼肌医学知识讲座,第10页,Filaments,骨骼肌医学知识讲座,第11页,Myosin,肌凝蛋白,Myosin filament(thick filament),粗肌丝,骨骼肌医学知识讲座,第12页,Actin,肌纤蛋白,Tropomyosin,原肌凝蛋白,Troponin,肌钙蛋白,Actin filament(thin filament),细肌丝,骨骼肌医学知识讲座,第13页,Titin,肌联蛋白,骨骼肌医学知识讲座,第14页,Sarcotubular system,(1)Transverse Tubule,横管,(2)Longitudinal Tubule,纵管,Sarcoplasmic reticulum,肌浆网,骨骼肌医学知识讲座,第15页,Molecular mechanisms of contraction,Sliding-filament mechanism,骨骼肌医学知识讲座,第16页,Contraction(shortening):,myosin binds to actin,and slides it,pulling the Z-lines closer together,and reducing the width of the I-bands.,Note that filament lengths have not changed.,骨骼肌医学知识讲座,第17页,Contraction:,myosins cross-bridges,（横桥）,bind to actin;,the crossbridges then flex to slide actin.,骨骼肌医学知识讲座,第18页,Click here to play the,Sarcomere Shortening,Flash Animation,骨骼肌医学知识讲座,第19页,The thick filament called myosin is actually a,polymer of myosin molecules,each of which,has a flexible cross-bridge that binds ATP and actin.,骨骼肌医学知识讲座,第20页,The cross-bridge cycle,requires ATP,The myosin-binding site on actin becomes available,so the energized cross-bridge binds.,1.,The full hydrolysis,and departure of ADP+P,i,causes the flexing of the bound cross-bridge.,2.,Binding of a“new”ATP,to the cross-bridge,uncouples the bridge.,3.,Partial,hydrolysis of,the bound ATP,energizes,or“re-cocks”,the bridge.,4.,骨骼肌医学知识讲座,第21页,The myosin-binding site on actin becomes available,so the energized cross-bridge binds.,1.,骨骼肌医学知识讲座,第22页,The full hydrolysis,and departure of ADP+P,i,causes the flexing of the bound cross-bridge.,2.,骨骼肌医学知识讲座,第23页,Binding of a“new”ATP,to the cross-bridge,uncouples the bridge.,3.,骨骼肌医学知识讲座,第24页,Partial,hydrolysis of,the bound ATP,energizes,or“re-cocks”,the bridge.,4.,骨骼肌医学知识讲座,第25页,The cross-bridge cycle,requires ATP,The myosin-binding site on actin becomes available,so the energized cross-bridge binds.,1.,The full hydrolysis,and departure of ADP+P,i,causes the flexing of the bound cross-bridge.,2.,Binding of a“new”ATP,to the cross-bridge,uncouples the bridge.,3.,Partial,hydrolysis of,the bound ATP,energizes,or“re-cocks”,the bridge.,4.,骨骼肌医学知识讲座,第26页,Click here to play the,Cross-bridge cycle,Flash Animation,骨骼肌医学知识讲座,第27页,In relaxed skeletal muscle,tropomyosin blocks,the cross-bridge binding site on actin.,Contraction occurs when calcium ions bind to,troponin;this complex then pulls tropomyosin,away from the cross-bridge binding site.,Roles of troponin,tropomyosin,and calcium in contraction,骨骼肌医学知识讲座,第28页,Interaction of myosin and actin,骨骼肌医学知识讲座,第29页,Transmission of action potential(AP)along T tubules,Calcium release caused by T tubule AP,Contraction initiated by calcium ions,Excitation-contraction coupling,兴奋,-,收缩偶联,骨骼肌医学知识讲座,第30页,The latent period between excitation and development,of tension in a skeletal muscle includes the time,needed to release Ca,+,from sarcoplasmic reticulum,move tropomyosin,and cycle the cross-bridges.,骨骼肌医学知识讲座,第31页,The transverse tubules bring,action potentials into the,interior of the skeletal muscle,fibers,so that the wave of,depolarization passes close,to the sarcoplasmic reticulum,stimulating the release of,calcium ions.,The extensive meshwork,of sarcoplasmic reticulum,assures that when it,releases calcium ions,they can readily diffuse,to all of the troponin sites.,骨骼肌医学知识讲座,第32页,Passage of an action potential along the transverse tubule opens nearby voltage-gated calcium channels,the“ryanodine receptor,”located on the sarcoplasmic reticulum,and,calcium ions released into the,cytosol bind to troponin.,The calcium-troponin complex“pulls”tropomyosin off the myosin-binding site of actin,thus allowing the binding of the cross-bridge,followed by its flexing to slide the actin filament.,骨骼肌医学知识讲座,第33页,骨骼肌医学知识讲座,第34页,Neuromuscular transmission,Excitation-contraction coupling,Muscle contraction,General process of excitation and contraction in skeletal muscle,骨骼肌医学知识讲座,第35页,A single motor unit,（运动单位）,consists of a motor neuron and all of the muscle fibers it controls.,骨骼肌医学知识讲座,第36页,The neuromuscular junction,（神经肌接头）,is the point of synaptic contact between the axon terminal of a motor neuron and the muscle fiber it controls.,Action potentials in the,motor neuron cause,Acetylcholine,（乙酰胆碱）,release into the neuromuscular junction.,Muscle contraction follows the delivery,of acetylcholine to the muscle fiber.,骨骼肌医学知识讲座,第37页,1.The exocytosis of acetylcholine from the axon terminal,occurs when the acetylcholine vesicles merge into the,membrane covering the terminal.,2.On the membrane of the muscle fiber,the receptors for,acetylcholine respond to its binding by increasing,Na,+,entry into the fiber,causing a graded depolarization.,3.The graded depolarization typically exceeds threshold for,the nearby voltage-gate Na,+,and K,+,channels,so an,action potential occurs on the muscle fiber.,骨骼肌医学知识讲座,第38页,Nicotinic acetylcholine receptor,烟碱型乙酰胆碱受体,Acetylcholinesterase,乙酰胆碱酯酶,骨骼肌医学知识讲座,第39页,End plate potential(EPP),终板电位,骨骼肌医学知识讲座,第40页,Miniature end plate potential,微终板电位,Small fluctuations(typically 0.5 mV)in the resting potential of postsynaptic cells.,They are the same shape as,but much smaller than,the end plate potentials caused by stimulation of the presynaptic cell.Miniature end plate potentials are considered as evidence for the quantal release of neurotransmitters at chemical synapses,a single miniature end plate potential resulting from the release of the contents of a single synaptic vesicle.,骨骼肌医学知识讲座,第41页,Click here to play the,Neuromuscular Junction,Flash Animation,骨骼肌医学知识讲座,第42页,Click here to play the,Action Potentials and,Muscle Contraction,Flash Animation,骨骼肌医学知识讲座,第43页,骨骼肌医学知识讲座,第44页,Muscle tension,肌张力,the force exerted on an object by a contracting muscle,Load,负荷,the force exerted on the muscle by an object(usually its weight),Isometric contraction,等长收缩,a muscle develops tension but does not shorten(or lengthen)(constant length),Isotonic contraction,等张收缩,the muscle shortens while the load on the muscle remains constant(constant tension),Mechanics of single-fiber contraction,骨骼肌医学知识讲座,第45页,The mechanical response of a single muscle fiber to a single action potential is know as a,TWITCH,Twitch contraction,单收缩,骨骼肌医学知识讲座,第46页,Tension increases rapidly and dissipates slowly,Shortening occurs slowly,only after taking up elastic tension;the relaxing muscle quickly returns to its resting length.,iso,=same,tonic,=tension,metric,=length,骨骼肌医学知识讲座,第47页,All three are isotonic contractions.,Latent period,潜伏期,Velocity of shortening,Duration of the twitch,Distance shortened,骨骼肌医学知识讲座,第48页,Load-velocity relation,长度,-,速度关系,骨骼肌医学知识讲座,第49页,Click here to play the,Mechanisms of,Single Fiber Contraction,Flash Animation,骨骼肌医学知识讲座,第50页,Complete dissipation of elastic tension,between subsequent stimuli.,S,3,occurred prior to,the complete dissipation,of elastic tension from S,2,.,S,3,occurred prior tothe dissipation of ANY,elastic tension from S,2,.,Frequency-tension relation,频率,-,张力关系,T e m p o r a l s u m m a t i o n.,骨骼肌医学知识讲座,第51页,Unfused tetanus,非融合性强直收缩,:,partial dissipation of,elastic tension between,subsequent stimuli.,Fused tetanus,融合性强直收缩,:,no time for dissipation,of elastic tension between,rapidly recurring stimuli.,Frequency-tension relation,骨骼肌医学知识讲座,第52页,Mechanism for greater tetanic tension,Successive action potentials result in a persistent elevation of cytosolic calcium concentration,骨骼肌医学知识讲座,第53页,Long sarcomere:,actin and myosin,do not overlap,much,so little,tension can be,developed.,Length-tension relation,Short sarcomere:,actin filaments,lack room to slide,so little tension can,be developed.,Optimal-length sarcomere:,lots of actin-myosin overlap,and plenty of room to slide.,Optimal length,骨骼肌医学知识讲座,第54页,Click here to play the,Length-Tension Relation,in Skeletal Muscles,Flash Animation,骨骼肌医学知识讲座,第55页,Skeletal muscles capacity to produce ATP via oxidative,phosphorylation is further supplemented by the availability,of molecular oxygen bound to intracellular myoglobin.,In skeletal muscle,ATP production via substrate phosphorylation,is supplemented by the availability of creatine phosphate,磷酸肌酸,.,骨骼肌医学知识讲座,第56页,In skeletal muscle,repetitive stimulation,leads to fatigue,疲劳,evident as,reduced tension.,Rest overcomes,fatigue,but fatigue,will reoccur sooner,if inadequate recovery,time passes.,骨骼肌医学知识讲座,第57页,On the basis of maximal velocities of shortening,Fast fibers,快肌纤维,containing myosin with high ATPase activity(type II fibers),Slow fibers,慢肌纤维,-containing myosin with low ATPase activity(type I fibers),On the basis of major pathway to form ATP,Oxidative fibers,氧化型肌纤维,containing numerous mitochondria and having a high capacity for oxidative phosphorylation,also containing large amounts of myoglobin(red muscle fibers),Glycolytic fibers,糖酵解型肌纤维,-containing few mitochondria but possessing a high concentration of glycolytic enzymes and a large store of glycogen,and containing little myoglobin(white muscle fibers),Types of skeletal muscle fibers,骨骼肌医学知识讲座,第58页,Slow-oxidative fibers,combine low myosin-ATPase activity with high oxidative capacity,Fast-oxidative fibers,-combine high myosin-ATPase activity with high oxidative capacity and intermediate glycolytic capacity,Fast-glycolytic fibers,-combine high myosin-ATPase activity with high glycolytic capacity,Types of skeletal muscle fibers,骨骼肌医学知识讲座,第59页,Slow-oxidative skeletal muscle,responds well to repetitive,stimulation without becoming,fatigued;muscles of body,posture are examples.,Fast-oxidative skeletal muscle,responds quickly,and,to,repetitive stimulation without,becoming fatigued;muscles,used in walking are examples.,Fast-glycolytic skeletal muscle,is used for quick bursts of,strong activation,such as,muscles used to jump or to,run a short sprint.,Most skeletal muscles include,all,three,types.,骨骼肌医学知识讲座,第60页,Note:Because fast-glycolytic fibers have significant glycolytic capacity,they are,sometimes called“fast oxidative-glycolytic FOG fibers.,骨骼肌医学知识讲座,第61页,All,three,types,of,muscle fibers,are represented,in a typical,skeletal muscle,and,under tetanic,stimulation,make the predicted,contributions to,the development,of muscle tension.,Slow-oxidative,Fast-oxidative,Fast-,glycolytic,Whole-muscle contraction,骨骼肌医学知识讲座,第62页,骨骼肌医学知识讲座,第63页,Flexors,（屈肌）,and extensors,（伸肌）,work in antagonistic,sets to refine movement,and to allow force,generation in two opposite directions.,骨骼肌医学知识讲座,第64页,How can gastrocnemius contraction result in two different movements?,骨骼肌医学知识讲座,第65页,The lever system of muscles and bones:,Here,muscle contraction must generate 70 kg force to hold a 10 kg object that is 30 cm away from the site of muscle attachment.,骨骼肌医学知识讲座,第66页,Muscle contraction that moves the,attachment site on bone 1 cm,results in a 7 cm movement of,the object 30 cm away from the site;,similar gains in movement velocity occur.,骨骼肌医学知识讲座,第67页,Duchenne muscular dystrophy,（,Duchenne,型肌营养不良）,weakens the hip and trunk muscles,thus altering the,lever-system relationships of the muscles,and bones that are used to stand up.,骨骼肌医学知识讲座,第68页,Thank,you!,骨骼肌医学知识讲座,第69页,