《基础医学各论I：骨骼肌》由会员分享，可在线阅读，更多相关《基础医学各论I：骨骼肌（88页珍藏版）》请在金锄头文库上搜索。
1、Skeletal Muscle骨骼肌骨骼肌Types of muscle: Skeletal muscle骨骼肌Cardiac muscle 心肌Smooth muscle平滑肌Striated muscle横纹肌MuscleMuscle (cont.)The sliding filament mechanism（肌丝滑行机制）（肌丝滑行机制）, in which myosin（肌凝蛋白）（肌凝蛋白） filaments bind to and move actin （肌纤（肌纤蛋白）蛋白）filaments, is the basis for shortening of stimulated
2、 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).Neuronal influences on the contractio
3、n 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.)Structure of skeletal muscleSkeletal muscles are a
4、ttached to the skeleton by tendons.Skeletal muscles typically contain many, many muscle fibers.The sarcomere（肌小节）（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 .A cross section through a sarcomere shows tha
5、t:each myosin can interact with 6 actin filaments, andeach actin can interact with 3 myosin filaments.Sarcomere structures in an electron micrograph.FilamentsMyosin肌凝蛋白 Myosin filament (thick filament)粗肌丝粗肌丝Actin肌纤蛋白Tropomyosin原肌凝蛋白Troponin肌钙蛋白Actin filament (thin filament)细肌丝细肌丝Titin肌联蛋白Sarcotubula
6、r system(1) Transverse Tubule横管(2) Longitudinal Tubule纵管Sarcoplasmic reticulum肌浆网Molecular mechanisms of contractionSliding-filament mechanismContraction (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
7、 lengths have not changed.Contraction: myosins cross-bridges（横桥）（横桥） bind to actin; the crossbridges then flex to slide actin.Click here to play theSarcomere ShorteningFlash AnimationThe thick filament called myosin is actually a polymer of myosin molecules, each of which has a flexible cross-bridge
8、 that binds ATP and actin.The cross-bridge cyclerequires ATPThe myosin-binding site on actin becomes available, so the energized cross-bridge binds.1.The full hydrolysis and departure of ADP + Pi causes the flexing of the bound cross-bridge.2.Binding of a “new” ATPto the cross-bridge uncouples the b
9、ridge.3. Partial hydrolysis of the bound ATP energizesor “re-cocks” the bridge.4.The myosin-binding site on actin becomes available, so the energized cross-bridge binds.1.The full hydrolysis and departure of ADP + Pi causes the flexing of the bound cross-bridge.2.Binding of a “new” ATPto the cross-b
10、ridge uncouples the bridge.3. Partial hydrolysis of the bound ATP energizesor “re-cocks” the bridge.4.The cross-bridge cyclerequires ATPThe myosin-binding site on actin becomes available, so the energized cross-bridge binds.1.The full hydrolysis and departure of ADP + Pi causes the flexing of the bo
11、und cross-bridge.2.Binding of a “new” ATPto the cross-bridge uncouples the bridge.3. Partial hydrolysis of the bound ATP energizesor “re-cocks” the bridge.4.Click here to play theCross-bridge cycleFlash AnimationIn relaxed skeletal muscle, tropomyosin blocksthe cross-bridge binding site on actin.Con
12、traction 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 contractionInteraction of myosin and actinTransmission of action potential (AP) along T tubulesCalcium release caused by T t
13、ubule APContraction initiated by calcium ionsExcitation-contraction coupling兴奋兴奋-收缩偶联收缩偶联The latent period between excitation and developmentof tension in a skeletal muscle includes the time needed to release Ca+ from sarcoplasmic reticulum, move tropomyosin, and cycle the cross-bridges. The transve
14、rse tubules bringaction potentials into the interior of the skeletal muscle fibers, so that the wave of depolarization passes closeto the sarcoplasmic reticulum,stimulating the release of calcium ions.The extensive meshworkof sarcoplasmic reticulum assures that when it releases calcium ions they can
15、 readily diffuseto all of the troponin sites.Passage of an action potential along the transverse tubule opens nearby voltage-gated calcium channels, the “ryanodine receptor,” located on the sarcoplasmic reticulum, andcalcium ions released into the cytosol bind to troponin. The calcium-troponin compl
16、ex “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.Which of these following proteins contains the binding sites for Ca2+ that initiates contraction? A Myosin B Troponin I C Tropomyosin D Trop
17、onin C E Troponin TNeuromuscular transmissionExcitation-contraction couplingMuscle contractionGeneral process of excitation and contraction in skeletal muscleA single motor unit（运动单位）（运动单位） consists of a motor neuron and all of the muscle fibers it controls. The neuromuscular junction（神经肌接头）（神经肌接头）i
18、s the point of synaptic contact between the axon terminal of a motor neuron and the muscle fiber it controls. Action potentials in themotor neuron cause Acetylcholine（乙酰胆碱）（乙酰胆碱） release into the neuromuscular junction.Muscle contraction follows the delivery of acetylcholine to the muscle fiber. 1.
19、The exocytosis of acetylcholine from the axon terminaloccurs when the acetylcholine vesicles merge into themembrane 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 depolariza
20、tion.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.Nicotinic acetylcholine receptor烟碱型乙酰胆碱受体烟碱型乙酰胆碱受体Acetylcholinesterase 乙酰胆碱酯酶乙酰胆碱酯酶End plate potential (EPP)终板电位终板电位Miniature end plate pot
21、ential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
22、 of neurotransmitters at chemical synapses, a single miniature end plate potential resulting from the release of the contents of a single synaptic vesicle.Click here to play theNeuromuscular JunctionFlash AnimationClick here to play theAction Potentials andMuscle ContractionFlash AnimationA woman co
23、mes to your clinic and explains that she is noting gradually worsening fatigue/weakness in her legs when she goes for her walk. She also mentions a droopy right eyelid, and wonders if this is a normal aging process. You examine her and find the following: overall decreased muscle strength, trace ref
24、lexes throughout, and weakness of eyelid closure bilaterally. The rest of the exam is unremarkable. What would you administer to treat the likely condition? A Muscarinic blockers B Nicotinic blockers C Acetylcholinesterase blockers D Alpha blockers E Beta blockersA woman comes to your clinic and exp
25、lains that she is noting gradually worsening fatigue/weakness in her legs when she goes for her walk. She also mentions a droopy right eyelid, and wonders if this is a normal aging process. You examine her and find the following: overall decreased muscle strength, trace reflexes throughout, and weak
26、ness of eyelid closure bilaterally. The rest of the exam is unremarkable. What would you administer to treat the likely condition? A Muscarinic blockers B Nicotinic blockers C Acetylcholinesterase blockers D Alpha blockers E Beta blockersNeuromuscular transmission A Is caused by the release of acety
27、lcholine from the muscle side of the junction B Shows a permeability change to Na+ and K+ at the receptor site during the endplate potential (EPP) C May be facilitated by curare in myasthenia gravis D Is blocked by curare because it competes with the Na+ entry during the muscle action potential E Is
28、 solely an electronic functionNeuromuscular transmission A Is caused by the release of acetylcholine from the muscle side of the junction B Shows a permeability change to Na+ and K+ at the receptor site during the endplate potential (EPP) C May be facilitated by curare in myasthenia gravis D Is bloc
29、ked by curare because it competes with the Na+ entry during the muscle action potential E Is solely an electronic functionA miniature end-plate potential is A Not related to changes in ionic permeability B A reduced action potential in the motor end-plate C Produced by spontaneous release of acetylc
30、holine D Responsible for weak muscular contractions E An afterdischarge at the neuromuscular junction A miniature end-plate potential is A Not related to changes in ionic permeability B A reduced action potential in the motor end-plate C Produced by spontaneous release of acetylcholine D Responsible
31、 for weak muscular contractions E An afterdischarge at the neuromuscular junction The action of acetylcholine at the neuromuscular junction is terminated primarily by A Enzymatic breakdown by choline acetylase B Enzymatic breakdown by acetylcholinesterase C Uptake into the muscle D Uptake into the n
32、erve ending E Diffusion into the surrounding extracellular fluidThe action of acetylcholine at the neuromuscular junction is terminated primarily by A Enzymatic breakdown by choline acetylase B Enzymatic breakdown by acetylcholinesterase C Uptake into the muscle D Uptake into the nerve ending E Diff
33、usion into the surrounding extracellular fluidThe transmission of an action potential over the muscle fiber membrane causes the contraction of the fiber a few milliseconds later. Which of the following terms is used to describe that process? A Ratchet Theory of Muscle Contraction B Excitation Contra
34、ction Coupling C Membrane Potential D All-or -Nothing LawThe transmission of an action potential over the muscle fiber membrane causes the contraction of the fiber a few milliseconds later. Which of the following terms is used to describe that process? A Ratchet Theory of Muscle Contraction B Excita
35、tion Contraction Coupling C Membrane Potential D All-or -Nothing LawMuscle tension 肌张力 the force exerted on an object by a contracting muscleLoad 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
36、) (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 contractionThe mechanical response of a single muscle fiber to a single action potential is know as a TWITCHTwitch contraction 单收缩单收缩Tension incr
37、eases rapidly and dissipates slowlyShortening occurs slowly, only after taking up elastic tension; the relaxing muscle quickly returns to its resting length.iso = same tonic = tension metric = lengthAll three are isotonic contractions. 1.Latent period潜伏期潜伏期2.Velocity of shortening3.Duration of the t
38、witch4.Distance shortened Load-velocity relation 长度长度-速度关系速度关系Click here to play theMechanisms ofSingle Fiber ContractionFlash AnimationAnswer the following question by referring to the attached chart. Which curve or line represents the total tension of the muscle? A Curve A B Curve B C Curve C D Cu
39、rve D E Curve EAnswer the following question by referring to the attached chart. Which curve or line represents the total tension of the muscle? A Curve A B Curve B C Curve C D Curve D E Curve EComplete dissipation of elastic tension between subsequent stimuli.S3 occurred prior tothe complete dissip
40、ation of elastic tension from S2.S3 occurred prior tothe dissipation of ANYelastic tension from S2.Frequency-tension relation频率频率-张力关系张力关系T e m p o r a l s u m m a t i o n.Unfused tetanus非融合性强直收缩非融合性强直收缩: partial dissipation of elastic tension between subsequent stimuli. Fused tetanus融合性强直收缩融合性强直收缩:
41、 no time for dissipation of elastic tension between rapidly recurring stimuli. Frequency-tension relationMechanism for greater tetanic tensionSuccessive action potentials result in a persistent elevation of cytosolic calcium concentrationLong sarcomere: actin and myosin do not overlap much, so littl
42、e tension can be developed.Length-tension relationShort 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 lengthClick here to play theLength-Tension Relationin Skeletal MusclesF
43、lash AnimationSkeletal 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 phos
44、phate磷酸肌酸磷酸肌酸. In skeletal muscle, repetitive stimulation leads to fatigue疲劳疲劳, evident as reduced tension. Rest overcomesfatigue, but fatigue will reoccur soonerif inadequate recoverytime passes. On the basis of maximal velocities of shorteningFast fibers快肌纤维 containing myosin with high ATPase acti
45、vity (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 ATPOxidative 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
46、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 fibersSlow-oxidative fibers combine low myosin-ATPase activity w
47、ith high oxidative capacityFast-oxidative fibers - combine high myosin-ATPase activity with high oxidative capacity and intermediate glycolytic capacityFast-glycolytic fibers - combine high myosin-ATPase activity with high glycolytic capacityTypes of skeletal muscle fibersSlow-oxidative skeletal mus
48、cle responds well to repetitive stimulation without becomingfatigued; muscles of bodyposture 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
49、bursts ofstrong activation, such as muscles used to jump or to run a short sprint. Most skeletal muscles include all three types. Note: Because fast-glycolytic fibers have significant glycolytic capacity, they are sometimes called “fast oxidative-glycolytic FOG fibers.Muscles containing many type II
50、A fibers are called A Red muscles B Slow oxidative muscles C White muscles D Fast glycolytic musclesMuscles containing many type IIA fibers are called A Red muscles B Slow oxidative muscles C White muscles D Fast glycolytic musclesThe store of glycogen in the muscle functions to A Attenuate blood gl
51、ucose levels directly B Provide energy for muscle contraction C Provide a source of ketone bodies D Provide structural integrity to muscle E Inhibit muscle contractionThe store of glycogen in the muscle functions to A Attenuate blood glucose levels directly B Provide energy for muscle contraction C
52、Provide a source of ketone bodies D Provide structural integrity to muscle E Inhibit muscle contractionAll three types of muscle fibersare represented in a typicalskeletal muscle, and, under tetanic stimulation,make the predicted contributions tothe development of muscle tension.Slow-oxidativeFast-o
53、xidative Fast-glycolyticWhole-muscle contractionFlexors（屈肌）（屈肌）and extensors（伸肌）（伸肌） work in antagonisticsets to refine movement,and to allow forcegeneration in two opposite directions.How can gastrocnemius contraction result in two different movements?The lever system of muscles and bones:Here, mus
54、cle contraction must generate 70 kg force to hold a 10 kg object that is 30 cm away from the site of muscle attachment.Muscle contraction that moves the attachment site on bone 1 cmresults in a 7 cm movement of the object 30 cm away from the site;similar gains in movement velocity occur.Duchenne mus
55、cular dystrophy（Duchenne型肌营养不良）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.Duchenne muscular dystrophy is a devastating, progressive disease that occurs in boys; it is characterized by the progressive necr
56、osis of skeletal muscle fibers and death at an average age of 16, usually from respiratory failure. It is the second most common genetic disorder in humans, and there is no specific treatment. The course of the disease includes slow muscular development, progressive weakness, and frequent contractur
57、es. The disease is usually recognized at ages 2 to 5, and the child is usually confined to a wheelchair by age 12. Laboratory observations show highly elevated serum concentrations of creatine kinase and other soluble sarcoplasmic enzymes. Both fast and slow muscle fibers are affected by fiber necro
58、sis and phagocytosis, balanced by marked regeneration of cells in the early stages of the disease. The fibers resemble fetal muscles, in terms of their isoenzyme patterns, with marked dedifferentiation. Fiber death and replacement by fat and connective tissue gradually predominate. DNA analysis reve
59、als that the disease is caused by the deficiency of a gene on the X chromosome. The product of the gene is a cytoskeletal protein called dystrophin that forms a network adjacent to the sarcolemma. Dystrophin is a very large protein (426 kDa). It is a minor constituent of muscle and links sarcomeres
60、to the sarcolemma via association with a glycoprotein inserted into the membrane. Case1. Diseases affecting striated muscle cells are uncommon but are devastating and characteristically lethal. Why? 2. What is the significance of the elevated serum creatine kinase level? 3. Is elevated serum creatin
61、e kinase diagnostic for muscular dystrophy? 4. Some muscles are more affected than others. In fact, the muscles of the calves exhibit a characteristic hypertrophy, whereas the muscles of the upper legs are weakened. What factors may influence differential responses in a patient whose skeletal muscle
62、 cells lack a functional dystrophin gene? 5. Why is Duchenne muscular dystrophy progressive even though the genetic defect is present from conception? 6. Why dont girls develop Duchenne muscular dystrophy? 7. Exercise is a major component of the clinical management of Duchenne muscular dystrophy. What is the rationale? 8. Would the introduction of a functional allele of the dystrophin gene in the affected cells be a potential treatment that could cure the disease?QuestionsThank you!
