肌肉结构课件.ppt

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1、Section 4Muscle ContractionShandong University，Institute of Physiology Shu-Yan Yu Shu-Yan Yu1 2Classification of the MuscleAccording to the structure:Striated Muscle,Smooth MuscleAccording to the nerve innervation:Voluntary Muscle,Involuntary MuscleAccording to the Function:Skeletal Muscle,Cardiac m

2、uscle,Smooth Muscle3Skeletal MuscleCardiac MuscleSmooth Muscle4Skeletal Muscle contraction under the control of CNS I:Signal Transmission Through the Neuromuscular Junction5 6Skeletal Muscle Innervation7Illustration of the Neuromuscular Junction(NMJ)89 Nerve Terminal:absence of myelination synaptic

3、vesicles:ACh Voltage-gated Ca2+channel10Motor end plate-1.N2-ACh receptor cation channel 2.acetylcholinesterase(乙酰胆碱酯酶乙酰胆碱酯酶)11New Ion Channel PlayersVoltage-gated Ca2+channel:in presynaptic nerve terminalmediates neurotransmitter releaseNicotinic Acetylcholine Receptor Channel:in muscle neuromuscul

4、ar junction(postsynaptic membrane,or end plate)mediates electrical transmission from nerve to muscle12Nerve Terminal Ca2+channelsStructurally similar to Na+channelsFunctionally similar to Na+channels except:activation occurs at more positive potentialsactivation and inactivation much slower than Na+

5、channels13Neuromuscular TransmissionSkeletal MuscleMyelinAxonAxon Terminal14Neuromuscular Transmission:Step by StepNerve actionpotential invadesaxon terminal-+-+-+Depolarizationof terminalopens Ca channelsLookhere+15K+OutsideInsideNa+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+K+K+K+K+K+K+K+K+K+K+K+AChAChAChCa

6、2+induces fusion ofvesicles with nerveterminal membrane.ACh is released anddiffuses acrosssynaptic cleft.(Quantal relaese)AChACh binds to itsreceptor on thepostsynaptic membraneBinding of ACh openschannel pore that ispermeable to Na+and K+.Na+Na+K+Muscle membraneNerveterminalCa2+Ca2+16End Plate Pote

7、ntial(EPP):50mVOutsideInsideMuscle membranePresynapticterminalMuscle MembraneVoltage(mV)Time(msec)-90 mVVKVNa0ThresholdPresynaptic APEPPThe movement of Na+and K+depolarizes muscle membranepotential(EPP)ACh Receptor ChannelsVoltage-gatedNa ChannelsInward RectifierK Channels17voltage gated Na+channels

8、 voltage gated K+channelsexcitation(action potential)thresholdNaNa+MEPP:0.4 mVEPP:50mV 50/0.4=125个囊泡个囊泡18Meanwhile.OutsideInsideAChACh unbinds fromits receptorMuscle membraneAChso the channel closesAChAChNerveterminalACh is hydrolyzed byAChE into Cholineand acetateCholineAcetateCholine is taken upin

9、to nerve terminalCholineCholine resynthesizedinto ACh and repackagedinto vesicleACh19transmittion2021Structural Reality22Neuromuscular TransmissionProperties of neuromuscular junction 1:1 transmission:A chemical transmission which is designed to assure that every presynaptic action potential results

10、 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 factorsThe NMJ is a site of considerable clinical importance23Clinical ChemistryAch is the naturalagonist at the neuromuscularjunction.Tubocurarine is t

11、heprimary paralyticingredient in curare.Tubocurarine competeswith ACh for bindingto receptor-but doesnot open the pore.So tubocurarine is aneuromuscularblocking agent.Tubocurarine and other,related compoundsare used to paralyzemuscles during surgery.Carbachol is asynthetic agonistnot hydrolyzed byac

12、etylcholinesterase.Carbachol and relatedcompounds are usedclinically for GI disorders,glaucoma,salivarygland malfunction,etc.Suberyldicholine is asynthetic neuromuscularagonist.Related compounds areuseful in the neuroscienceresearch24Anticholinesterase AgentsAnticholinesterase(anti-ChE)agents inhibi

13、t acetylcholinesterase（乙酰胆碱酯酶）prolong excitation at the NMJ251.Normal:ACh Choline+Acetate AChE2.With anti-AchE:ACh Choline+Acetate anti-AChEAnticholinesterase Agents26Uses of anti-ChE agentsClinical applications(Neostigmine,新斯的明,Physostigmine毒扁豆碱)Insecticides(organophosphate 有机磷酸酯)Nerve gas(e.g.Sari

14、n 沙林，甲氟膦酸异丙酯。一种用作神经性毒气的化学剂)27Sarin 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

15、 and sending more than 5,000 others to hospitals.28东京地铁毒气案东京地铁毒气案（1995年）年）“奥姆真理教奥姆真理教”造成造成12人死亡，人死亡，14人终身残疾，人终身残疾，5500多人受伤的惨剧多人受伤的惨剧29SarinSarin,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 e

16、xperts say that sarin gas is 500 times more toxic than cyanide（氢化物）gas.30NMJ DiseasesMyasthenia Gravis（重症肌无力）Autoimmunity to ACh receptorFewer functional ACh receptorsLow“safety factor”for NM transmissionLambert-Eaton syndrome（兰伯特-伊顿综合征，癌性肌无力综合征）Autoimmunity directed against Ca2 channelsReduced ACh

17、releaseLow“safety factor”for NM transmissionII:Microstructure of Skeletal Muscle31 32Skeletal MuscleHuman body contains over 400 skeletal muscles40-50%of total body weightFunctions of skeletal muscleForce production for locomotion and breathingForce production for postural supportHeat production dur

18、ing cold stress33Fascicles（肌束）（肌束）:bundles,CT(connective tissue)covering on each oneMuscle fibers:muscle cells34 Myofibril（肌原纤维）（肌原纤维）musle fiber:muscle cellSarcolemma（肌管系统）（肌管系统）35Structure of Skeletal Muscle:muscle cellsSarcolemma（肌管系统）Transverse(T)tubuleLongitudinal tubule(Sarcoplasmic reticulum,

19、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)36Sarcolemma：肌管系统肌管系统37Sarcolemma Transverse tubulesSarcoplasmic reticulum-Storage sites for calciumTerminal cisternae-Storage sites for calcium38Triad（三联管）triad纵管（肌质网纵管（肌质网,SR）横管（横管（T管）管）在肌原

20、纤维周围的在肌原纤维周围的SR也称为也称为纵行肌质网（纵行肌质网（L SR）连接内质网（连接内质网（JSR、终池）、终池）39 myofibril：肌原纤维肌原纤维40Sarcomeres(肌小节肌小节)Sarcomere:bundle of alternating thick and thin filaments Sarcomeres join end to end to form myofibrilsThousands per fiber,depending on length of muscleAlternating thick and thin filaments create app

21、earance of striations4142 filamentsthick filamentsthin filaments 43Myosin head is hinged Bends and straightens during contractionThick filaments：Myosin 肌球蛋白肌球蛋白44 to ATP to actin 肌动蛋白肌动蛋白 （细肌丝）（细肌丝）Thick filaments：myosin myosin 45Thick filaments(myosin)Bundle of myosin proteins shaped like double-he

22、aded golf clubsMyosin heads have two binding sitesActin binding site forms cross bridgeNucleotide binding site binds ATP(Myosin ATPase)Hydrolysis of ATP provides energy to generate power stroke46Thin filaments47Thin filaments Backbone:two strands of polymerized globular actin fibrous actin（肌纤蛋白，肌纤蛋白

23、，肌动蛋白肌动蛋白）Each actin has myosin binding siteTroponin（肌钙蛋白肌钙蛋白）Binds Ca2+;regulates muscle contractionTropomyosin（原肌球蛋白）原肌球蛋白）Lies in groove of actin helixBlocks myosin binding sites in absence of Ca2+48 Thin filament binding site to cross bridgea.Actin molecules Backbone:Each actin has myosin bindin

24、g siteActin49 Thin filament b.Tropomyosin 原原肌球蛋白肌球蛋白 actinbinding site to cross bridge Blocks myosin binding sites in absence of Ca2+Tropomyosin50 Thin filament c.TroponinTroponin：肌钙蛋白肌钙蛋白 Binds Ca2+;TropomyosinActinTroponin51Thin filament 原肌球蛋白原肌球蛋白肌钙蛋白肌钙蛋白肌动蛋白肌动蛋白（收缩蛋白质）（收缩蛋白质）52Thick filament:Myo

25、sin(head and tail)Thin filament:Actin,Tropomyosin,Troponin(calcium binding site)Thick filamentActinThin filamentTroponinTropomyosin53 III：Molecular Mechanism of Muscular ContractionThe sliding filament modelMuscle shortening is due to movement of the actin filament over the myosin filamentReduces th

26、e distance between Z-lines54The Sliding Filament Model of Muscle Contraction55Changes in the appearance of a Sarcomere during the Contraction of a Skeletal Muscle Fiber56Cross-Bridge Formation in Muscle Contraction57Energy for Muscle ContractionATP is required for muscle contractionMyosin ATPase bre

27、aks down ATP as fiber contracts58Nerve Activation of Individual Muscle Cells (cont.)59Action potential along T-tubule causes release of calcium from cisternae of TRIADCross-bridge cycleExcitation/contraction couplingCross-bridge cycle 60 61Before:Myosin heads form cross bridgesMyosin head is tightly

28、 bound to actin in rigor stateNothing bound to nucleotide binding site62 Before:ATP binds to myosinMyosin changes conformation,releases actin63Cycle Begin:1.ATP hydrolysisATP is broken down into:ADP+Pi(inorganic phosphate)Both ADP and Pi remain bound to myosin64 Myosin head changes conformationMyosi

29、n head rotates and face to new actin moleculeMyosin is in high energy configuration65Ca2+in sarcoplasmic increased,Ca2+binds to Troponin（肌钙蛋白肌钙蛋白）;Myosin head bind to actin;2.Myosin head bind to actin663.Power strokeHead pushes on actin filament and causes sliding(retched action)Release of ADP and P

30、i from myosin head(from high energy state)(Myosin head splits ATP and bends toward H zone.This is Power stroke.)67ATP binds to myosinATP binds to myosinMyosin changes conformation,releases actinMyosin head rotates and face to new actinReady to repeat cycle4.Crossbridge detachment and energised68 cro

31、ss bridge cyclecross bridge cycleRelaxed state69 Crossbridge attachmentSteps in a cross bridge cycleRelaxed state70 Crossbridge attachmentSteps in a cross bridge cycleRelaxed stateTension develops 71 Crossbridge attachmentSteps in a cross bridge cycleTension develops Crossbridge detachment Crossbrid

32、ge energisedCa2+present72 Cross Bridge Cycle7374Rigor mortis（尸僵）（尸僵）Myosin cannot release actin until a new ATP molecule bindsRun out of ATP at death,cross-bridges never release75Many contractile cycles occur asynchronously during a single muscle contractionNeed steady supply of ATP!76Regulation of

33、ContractionTropomyosin blocks myosin binding in absence of Ca2+Low intracellular Ca2+when muscle is relaxed77Ca+2 binds to troponin during contractionTroponin-Ca+2 pulls tropomyosin,unblocking myosin-binding sitesMyosin-actin cross-bridge cycle can now occur78How does Ca2+get into cell?Action potent

34、ial releases intracellular Ca2+from sarcoplasmic reticulum(SR)SR is modified endoplasmic reticulumMembrane contains Ca2+pumps to actively transport Ca2+into SRMaintains high Ca2+in SR,low Ca2+in cytoplasmThe action potential triggers contractionHow does the AP trigger contraction?This question has t

35、he 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 Cai?how does an increase in Cai cause contraction?79Z discA band(myosin)I band(actin)Z discM lineZ discsarcoplasmicreticulumt

36、-tubulesjunctional feetTriadContractile 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)proteinsThe association of a t-tubule with SR on either side is often called a triad

37、（三联管三联管）(tri meaning three)Structures involved in EC coupling80Structures involved in EC coupling-Skeletal Muscle-outinvoltage sensor?junction footsarcoplasmic reticulumsarcolemmaT-tubule8182Ca2+Controls ContractionCa2+Channels and Pumps Release of Ca2+from the SR triggers contraction Reuptake of Ca

38、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 Ca2+channel activity8384Dihydropyridine Receptor（双氢吡啶双氢吡啶）-L-Ca2+channel In t-tubules of heart and skeletal muscle Nifedipine and other DHP-like molecules

39、 bind to the DHP receptor in t-tubules In heart,DHP receptor is a voltage-gated Ca2+channel In skeletal muscle,DHP receptor is apparently a voltage-sensing protein and probably undergoes voltage-dependent conformational changes 85Ryanodine ReceptorThe foot structure in terminal cisternae of SR Foot

40、structure is a Ca2+channel of unusual design Conformation change or Ca2+-channel activity of L-Ca2+channel（DHP receptor）apparently gates the ryanodine receptor,opening and closing Ca2+channels Many details are yet to be elucidated!outinvoltage sensor(DHP receptor)junctional foot(ryanodine receptor)s

41、arcoplasmic reticulumsarcolemmaT-tubuleSkeletal muscleThe AP:moves down the t-tubulevoltage change detected by L-Ca2+channel L-Ca2+channel is essentially a voltage-gated Ca2+channelis communicated to the ryanodine receptor which opens to allow Ca2+out of SR activates contraction8687Cardiac muscleThe

42、 AP:moves down the t-tubulevoltage change detected by L-Ca2+channel which opens to allow small amount of(trigger)Ca2+into the fibreCa2+binds to ryanodine receptors which open to release a large amount of(activator)Ca2+(CACR)Thus,calcium,not voltage,appears to trigger Ca2+release in Cardiac muscle!ou

43、tinvoltage sensor&Ca channel(DHP receptor)junctional foot(ryanodine receptor)sarcoplasmic reticulumsarcolemmaT-tubule8889The 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-Ca2+channel)The ryanodine

44、 receptor is the SR Ca release channelCa2+release is proportional to membrane voltageCardiacThe trigger for SR release appears to be calcium(Calcium Activated Calcium Release-CACR)The t-tubule membrane has a Ca2+channel(L-Ca2+channel)The ryanodine receptor is the SR Ca release channelThe ryanodine r

45、eceptor is Ca-gated&Ca release is proportional to Ca2+entry 9091Transverse tubules connect plasma membrane of muscle cell to SR92Ca2+release during Excitation-Contraction couplingRyanodyne RCa-release ch.Action potential on motor endplate travels down T tubules93Voltage-gated Ca2+channels open,Ca2+f

46、lows out SR into cytoplasmCa2+channels close when action potential ends.Active transport pumps continually return Ca2+to SRCa ATPase(SERCA)94Excitation-Contraction CouplingDepolarization of motor end plate(excitation)is coupled to muscular contractionNerve impulse travels along sarcolemma and down T

47、-tubules to cause a release of Ca2+from SRCa2+binds to troponin and causes position change in tropomyosin,exposing active sites on actinPermits strong binding state between actin and myosin and contraction occursATP is hydrolyzed and energy goes to myosin head which releases from actin95Summary:Exci

48、tation-Contraction CouplingIV:Factors that Affect the Efficiency of Muscle Contraction96 97Tension and LoadThe force exerted on an object by a contracting muscle is known as tension.The force exerted on the muscle by an object(usually its weight)is termed load.According to the time of effect exerted

49、 by the loads on the muscle contraction，the load was divided into two forms,preload and afterload.981.PreloadPreload is a load on the muscle before muscle contraction.Determines the initial length of the muscle before contraction.Initial length is the length of the muscle fiber before its contractio

50、n.It is positively proportional to the preload.99The Effect of Sarcomere Length on TensionThe Length Tension Curve(长度长度-张力曲线）张力曲线）Concept of optimal length1001012.AfterloadAfterload is a load on the muscle after the beginning of muscle contraction.The reverse force that oppose the contractile force