肌肉结构课件.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,*,Section 4,Muscle Contraction,Shandong University,，,Institute of Physiology,Shu-Yan Yu,1,2,Classification of the Muscle,According to the,structure,:Striated Muscle,Smooth Muscle,According to the,nerve innervation,:Voluntary Muscle,Involuntary Muscle,According to the,Function,:Skeletal Muscle,Cardiac muscle,Smooth Muscle,3,Skeletal Muscle,Cardiac Muscle,Smooth Muscle,4,Skeletal Muscle,contraction under the control of CNS,I:Signal Transmission Through the Neuromuscular Junction,5,6,Skeletal Muscle Innervation,7,Illustration of the Neuromuscular Junction(NMJ),8,9,Nerve Terminal,:,absence of myelination,synaptic vesicles,:ACh,Voltage-gated Ca,2+,channel,10,Motor end plate,-,1.N,2,-ACh receptor cation channel,2.,acetylcholinesterase,(,乙酰胆碱酯酶,),11,New Ion Channel Players,Voltage-gated Ca,2+,channel,:,in presynaptic nerve terminal,mediates neurotransmitter release,Nicotinic Acetylcholine Receptor Channel,:,in muscle neuromuscular junction(postsynaptic membrane,or end plate),mediates electrical transmission from nerve to muscle,12,Nerve Terminal Ca,2+,channels,Structurally similar to Na,+,channels,Functionally similar to Na,+,channels except:,activation occurs at,more,positive potentials,activation and inactivation,much slower,than Na,+,channels,13,Neuromuscular Transmission,Skeletal,Muscle,Myelin,Axon,Axon Terminal,14,Neuromuscular,Transmission:,Step by Step,Nerve action,potential invades,axon terminal,-,+,-,-,-,-,-,-,+,+,+,+,+,+,+,-,-,-,+,+,Depolarization,of terminal,opens Ca channels,Look,here,+,15,K,+,Outside,Inside,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,Na,+,K,+,K,+,K,+,K,+,K,+,K,+,K,+,K,+,K,+,K,+,K,+,ACh,ACh,ACh,Ca,2+,induces fusion of,vesicles with nerve,terminal membrane.,ACh is released and,diffuses across,synaptic cleft.(Quantal relaese),ACh,ACh binds to its,receptor on the,postsynaptic membrane,Binding of ACh opens,channel pore that is,permeable to Na,+,and K,+,.,Na,+,Na,+,K,+,Muscle membrane,Nerve,terminal,Ca,2+,Ca,2+,16,End Plate Potential(EPP):50mV,Outside,Inside,Muscle membrane,Presynaptic,terminal,Muscle Membrane,Voltage(mV),Time(msec),-90 mV,V,K,V,Na,0,Threshold,Presynaptic,AP,EPP,The movement of Na,+,and K,+,depolarizes muscle membrane,potential(EPP),ACh Receptor Channels,Voltage-gated,Na Channels,Inward Rectifier,K Channels,17,voltage gated Na,+,channels voltage gated K,+,channels,excitation(action potential),threshold,Na,+,MEPP:0.4 mV,EPP:50mV,50/0.4=125,个囊泡,18,Meanwhile.,Outside,Inside,ACh,ACh unbinds from,its receptor,Muscle membrane,ACh,so the channel closes,ACh,ACh,Nerve,terminal,ACh is hydrolyzed by,AChE into Choline,and acetate,Choline,Acetate,Choline is taken up,into nerve terminal,Choline,Choline resynthesized,into ACh and repackaged,into vesicle,ACh,19,transmittion,20,21,Structural Reality,22,Neuromuscular Transmission,Properties of neuromuscular junction,1:1 transmission:,A chemical transmission which is designed to assure that every presynaptic action potential results in a postsynaptic one,An,unidirectional,process:,electrical-chenmical-electrical,Has a,time delay,:20nm/0.5-1ms,Is,easily affected,by drugs and some factors,The NMJ is a site of,considerable clinical importance,23,Clinical Chemistry,Ach is the natural,agonist at the,neuromuscular,junction.,Tubocurarine is the,primary paralytic,ingredient in curare.,Tubocurarine competes,with ACh for binding,to receptor-but does,not open the pore.,So tubocurarine is a,neuromuscular,blocking agent.,Tubocurarine and other,related compounds,are used to paralyze,muscles during surgery.,Carbachol is a,synthetic agonist,not hydrolyzed by,acetylcholinesterase.,Carbachol,and related,compounds are used,clinically for GI disorders,glaucoma,salivary,gland malfunction,etc.,Suberyldicholine is a,synthetic neuromuscular,agonist.,Related compounds are,useful in the neuroscience,research,24,Anti,cholinesterase Agents,Anticholinesterase(anti-ChE)agents,inhibit acetylcholinesterase,（乙酰胆碱酯酶）,prolong excitation,at the NMJ,25,1.Normal:,ACh,Choline+Acetate,AChE,2.With anti-AchE:,ACh,Choline+Acetate,anti-AChE,Anticholinesterase Agents,26,Uses of anti-ChE agents,Clinical applications,(Neostigmine,新斯的明,Physostigmine,毒扁豆碱,),Insecticides,(organophosphate,有机磷酸酯,),Nerve gas,(e.g.Sarin,沙林，,甲氟膦酸异丙酯,。,一种用作神经性毒气的化学剂),),27,Sarin and,Aum Shinrikyo(,奥姆真理教,),Aum Shinrikyo(,奥姆真理教,)is a Japanese religious cult obsessed with the apocalypse,（启示，天启）,.,The previously obscure group became infamous in 1995 when some of its members released deadly,sarin,nerve gas,into the Tokyo subway system,killing 12 people and sending more than 5,000 others to hospitals.,28,东京地铁毒气案,（,1995,年）,“,奥姆真理教”,造成,12,人死亡，,14,人终身残疾，,5500,多人受伤的惨剧,29,Sarin,Sarin,which comes in both liquid and gas forms,is a highly toxic and volatile nerve agent developed by Nazi scientists in Germany in the 1930s.,Chemical weapons experts say that sarin gas is 500 times more toxic than cyanide,（氢化物）,gas.,30,NMJ Diseases,Myasthenia Gravis,（重症肌无力）,Autoimmunity to,ACh receptor,Fewer functional ACh receptors,Low“safety factor”for NM transmission,Lambert-Eaton syndrome,（,兰伯特,-,伊顿综合征,，,癌性肌无力综合征,）,Autoimmunity directed against,Ca,2,channels,Reduced ACh release,Low“safety factor”for NM transmission,II,:,Microstructure of,Skeletal Muscle,31,32,Skeletal Muscle,Human body contains over 400 skeletal muscles,40-50%of total body weight,Functions of skeletal muscle,Force production for,locomotion and breathing,Force production for,postural support,Heat production during,cold stress,33,Fascicles,（肌束）,:bundles,CT(connective tissue)covering on each one,Muscle fibers,:muscle cells,34,Myofibril,（肌原纤维）,musle fiber,:,muscle cell,Sarcolemma,（肌管系统）,35,Structure of Skeletal Muscle:,muscle cells,Sarcolemma,（肌管系统）,Transverse(T)tubule,Longitudinal tubule(Sarcoplasmic reticulum,SR,肌浆网,),Myofibrils,（肌原纤维）,Actin,肌动蛋白,(,thin filament,),Troponin,（肌钙蛋白）,Tropomyosin,（原肌球蛋白）,Myosin,肌球蛋白,(,thick filament,),36,Sarcolemma,：,肌管系统,37,Sarcolemma,Transverse tubules,Sarcoplasmic reticulum,-Storage sites for calcium,Terminal cisternae,-Storage sites for calcium,38,Triad,（三联管）,triad,纵管（肌质网,SR,）,横管（,T,管）,在肌原纤维周围的,SR,也称为,纵行肌质网（,L SR,）,连接内质网（,JSR,、终池）,39,myofibril,：,肌原纤维,40,Sarcomeres,(,肌小节,),Sarcomere,:,bundle of alternating thick and thin filaments,Sarcomeres join end to end to form myofibrils,Thousands per fiber,depending on length of muscle,Alternating thick and thin filaments,create appearance of striations,41,42,filaments,thick filaments,thin filaments,43,Myosin head,is hinged,Bends,and,straightens,during contraction,Thick filaments,：,Myosin,肌球蛋白,44,to,ATP,to actin,肌动蛋白,（细肌丝）,Thick filaments,：,myosin,45,Thick filaments(myosin),Bundle of myosin proteins shaped like,double-headed golf clubs,Myosin heads have two binding sites,Actin binding site forms,cross bridge,Nucleotide binding site,binds ATP,(Myosin ATPase),Hydrolysis of ATP,provides energy,to generate,power stroke,46,Thin filaments,47,Thin filaments,Backbone,:,two strands of,polymerized,globular,actin,fibrous actin,（,肌纤蛋白，,肌动蛋白,）,Each actin has,myosin binding site,Troponin,（,肌钙蛋白,）,Binds Ca,2+,;,regulates muscle contraction,Tropomyosin,（,原肌球蛋白）,Lies in groove of actin helix,Blocks myosin binding sites,in absence of Ca,2+,48,Thin filament,binding site to cross bridge,a.,Actin molecules,Backbone,:,Each actin has,myosin binding site,Actin,49,Thin filament,b.,Tropomyosin,原,肌球蛋白,actin,binding site to cross bridge,Blocks myosin binding sites,in absence of Ca2+,Tropomyosin,50,Thin filament,c.,Troponin,：,肌钙蛋白,Binds Ca2+;,Tropomyosin,Actin,Troponin,51,Thin filament,原肌球蛋白,肌钙蛋白,肌动蛋白,（收缩蛋白质）,52,Thick filament,:Myosin(head and tail),Thin filament,:Actin,Tropomyosin,Troponin(calcium binding site),Thick filament,Actin,Thin,filament,Troponin,Tropomyosin,53,III,：,Molecular Mechanism of,Muscular Contraction,The sliding filament model,Muscle shortening is due to,movement of the actin filament over the myosin filament,Reduces the distance between Z-lines,54,The Sliding Filament Model of Muscle Contraction,55,Changes in the appearance of a Sarcomere during the Contraction of a Skeletal Muscle Fiber,56,Cross-Bridge Formation,in Muscle Contraction,57,Energy,for Muscle Contraction,ATP is required for muscle contraction,Myosin ATPase,breaks down ATP as fiber contracts,58,Nerve Activation,of Individual Muscle Cells,(,cont,.),59,Action potential along,T-tubule,causes,release of calcium,from cisternae of TRIAD,Cross-bridge cycle,Excitation/contraction coupling,Cross-bridge cycle,60,61,Before:,Myosin heads form cross,bridges,Myosin head is tightly bound to actin in rigor state,Nothing bound to nucleotide binding site,62,Before:,ATP binds to myosin,Myosin changes conformation,releases actin,63,Cycle Begin:,1.ATP hydrolysis,ATP is broken down,into:,ADP+P,i,(inorganic phosphate),Both ADP and P,i,remain bound to myosin,64,Myosin head changes conformation,Myosin head,rotates and face to,new actin molecule,Myosin is in,high energy configuration,65,Ca,2+,in s,arcoplasmic,increased,Ca,2+,binds,to Troponin,（,肌钙蛋白,）,;,Myosin head,bind,to actin,;,2.,Myosin head bind,to actin,66,3.Power stroke,Head pushes on actin filament and,causes sliding,(retched action),Release of,ADP,and P,i,from myosin head(from high energy state),(,Myosin head splits ATP and bends toward H zone.This is,Power stroke,.,),67,ATP binds to myosin,Myosin changes conformation,releases actin,Myosin head rotates and,face to new actin,Ready to repeat cycle,Crossbridge detachment and energised,68,cross bridge cycle,Relaxed state,69,Crossbridge attachment,Steps in,a cross bridge cycle,Relaxed state,70,Crossbridge attachment,Steps in,a cross bridge cycle,Relaxed state,Tension develops,71,Crossbridge attachment,Steps in,a cross bridge cycle,Tension develops,Crossbridge detachment,Crossbridge energised,Ca,2+,present,72,Cross Bridge Cycle,73,74,Rigor mortis,（尸僵）,Myosin cannot release actin until a new ATP molecule binds,Run out of ATP at death,cross-bridges never release,75,Many contractile cycles,occur,asynchronously,during a single muscle contraction,Need steady supply of,ATP!,76,Regulation of Contraction,Tropomyosin blocks myosin binding in absence of,Ca,2+,Low intracellular Ca,2+,when muscle is relaxed,77,Ca,+2,binds to troponin during contraction,Troponin-Ca,+2,pulls tropomyosin,unblocking myosin-binding sites,Myosin-actin cross-bridge cycle can now occur,78,How does,Ca,2+,get into cell?,Action potential,releases intracellular Ca,2+,from sarcoplasmic reticulum(SR),SR is modified endoplasmic reticulum,Membrane contains,Ca,2+,pumps,to actively transport Ca,2+,into SR,Maintains,high Ca,2+,in SR,low Ca,2+,in cytoplasm,The action potential triggers contraction,How does the AP trigger contraction?,This question has the beginning(AP)and the end(contraction)but it misses lots of things in the middle!,We should ask:,how does the AP cause release of,Ca2+,from the SR,so leading to an increase in Ca,i,?,how does an increase in Ca,i,cause contraction?,79,Z disc,A band,(myosin),I band,(actin),Z disc,M line,Z disc,sarcoplasmic,reticulum,t-tubules,junctional feet,Triad,Contractile proteins in striated muscle are organised into,sarcomeres,T-tubules and sarcoplasmic reticulum are organised so that,Ca2+,release,is directed toward,the regulatory(,Ca2+,binding)proteins,The association of a t-tubule with SR on either side is often called a,triad,（,三联管,）,(,tri,meaning three),Structures involved in EC coupling,80,Structures involved in EC coupling-,Skeletal Muscle-,out,in,voltage sensor?,junction foot,sarcoplasmic,reticulum,sarcolemma,T-tubule,81,82,Ca,2+,Controls Contraction,Ca,2+,Channels and Pumps,Release of Ca,2,+,from the SR triggers,contraction,Reuptake of Ca,2+,into SR,relaxes,muscle,So how is calcium released in response to nerve impulses?,Answer has come from studies of antagonist molecules that block,Ca,2+,channel activity,83,84,Dihydropyridine Receptor,（,双氢吡啶,）,-,L-,Ca,2+,channel,In,t-tubules,of heart and skeletal muscle,Nifedipine and other DHP-like molecules bind to the DHP receptor in t-tubules,In heart,DHP receptor is a,voltage-gated Ca,2+,channel,In,skeletal muscle,DHP receptor is apparently a,voltage-sensing protein,and probably undergoes voltage-dependent,conformational changes,85,Ryanodine Receptor,The foot structure in,terminal cisternae,of SR,Foot structure is a,Ca,2+,channel,of unusual design,Conformation change or Ca,2+,-channel activity of,L-,Ca,2+,channel,（,DHP receptor,）,apparently,gates the ryanodine receptor,opening and closing Ca,2+,channels,Many details are yet to be elucidated!,out,in,voltage sensor,(DHP receptor),junctional foot,(ryanodine receptor),sarcoplasmic,reticulum,sarcolemma,T-tubule,Skeletal muscle,The AP:,moves down the t-tubule,voltage change detected by,L-,Ca,2+,channel,L-,Ca,2+,channel,is essentially a voltage-gated,Ca,2+,channel,is,communicated to the,ryanodine receptor,which opens to allow,Ca,2+,out of SR,activates contraction,86,87,Cardiac muscle,The AP:,moves down the t-tubule,voltage change detected by,L-,Ca,2+,channel,which opens to allow small amount of(trigger),Ca,2+,into the fibre,Ca,2+,binds to ryanodine receptors,which open to release a large amount of(activator),Ca,2+,(CACR),Thus,calcium,not voltage,appears to,trigger,Ca,2+,release,in Cardiac muscle!,out,in,voltage sensor,&Ca channel,(DHP receptor),junctional foot,(ryanodine receptor),sarcoplasmic,reticulum,sarcolemma,T-tubule,88,89,The Answers!,Skeletal,The trigger for SR release appears to be,voltage,(Voltage Activated Calcium Release-VACR),The t-tubule membrane has a,voltage sensor,(,L-,Ca,2+,channel,),The ryanodine receptor is the SR Ca release channel,Ca,2+,release is,proportional to membrane voltage,Cardiac,The trigger for SR release appears to be,calcium,(Calcium Activated Calcium Release-CACR),The t-tubule membrane has a,Ca,2+,channel,(,L-Ca,2+,channel,),The ryanodine receptor is the SR Ca release channel,The ryanodine receptor is Ca-gated&Ca release is,proportional to Ca,2+,entry,90,91,Transverse tubules,connect plasma membrane of muscle cell to SR,92,Ca,2+,release during,Excitation-Contraction coupling,Ryanodyne R,Ca-release ch.,Action potential on motor endplate,travels down T tubules,93,Voltage-gated Ca,2+,channels open,Ca,2+,flows out SR into cytoplasm,Ca,2+,channels close when action potential ends.Active transport pumps continually return Ca,2+,to SR,Ca ATPase,(SERCA),94,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,95,Summary:Excitation-Contraction Coupling,IV:Factors that Affect the Efficiency of Muscle Contraction,96,97,Tension and Load,The force exerted on an object by a contracting muscle is known as,tension,.,The force exerted on the