英文医学课件：1 骨骼肌-赖蒽茵 140923

1、Skeletal Muscle,Types of muscle: Skeletal muscle骨骼肌 Cardiac muscle 心肌 Smooth muscle平滑肌,Striated muscle 横纹肌,Muscle,Muscle contraction,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, smo

2、oth, 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 contraction of muscles i

3、s 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 contraction,内脏,Structure of skeletal muscle,Skeletal muscles are attac

4、hed to the skeleton by tendons.,Skeletal muscles typically contain many, many muscle fibers.,肌腱,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 .,Titin 肌联蛋白,Titin（肌联蛋白）:从细肌丝的z发起，向粗肌丝内延伸并与M线接触，将粗

5、细肌丝连接在一起,A cross section of sarcomere: each myosin can interact with 6 actin filaments each actin can interact with 3 myosin filaments,Sarcomere structures in an electron micrograph.,Filaments,Myosin 肌凝蛋白,Myosin 肌凝蛋白,Myosin filament (thick filament)粗肌丝,Actin 肌纤蛋白 Tropomyosin 原肌凝蛋白 Troponin 肌钙蛋白,Acti

6、n filament (thin filament) 细肌丝,Sarcotubular system,(1) Transverse Tubule横管 (2) Longitudinal Tubule纵管 Sarcoplasmic reticulum肌浆网,肌膜,Molecular mechanisms of contraction,Contraction myosin binds to actin, pulling the Z-lines closer together, and reducing the width of the I-bands. filament lengths have n

7、ot changed,Contraction: myosins cross-bridges（横桥） bind to actin; the crossbridges then flex to slide actin.,Thick filament (myosin) is actually a polymer of myosin molecule which has a flexible cross-bridge that binds ATP and actin.,Cross-bridge cycle requires ATP,The myosin-binding site on actin be

8、comes available, so the energized cross-bridge binds.,1.,水解,The myosin-binding site on actin becomes available, so the energized cross-bridge binds.,1.,The myosin-binding site on actin becomes available, so the energized cross-bridge binds.,1.,Cross-bridge cycle requires ATP,In relaxed skeletal musc

9、le, 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,Interaction of myosin and actin,Myosin 肌凝蛋白 Ac

10、tin 肌纤蛋白,Transmission of action potential along T tubules Calcium release caused by T tubule action potential Contraction initiated by calcium ions,Excitation-contraction coupling 兴奋-收缩偶联,The latent period between excitation and development of tension in a skeletal muscle includes the time needed to

11、 release Ca+ from sarcoplasmic reticulum, move tropomyosin, and cycle the cross-bridges.,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.

12、,The extensive meshwork (网状) of sarcoplasmic reticulum assures that when it releases calcium ions they can readily diffuse to all of the troponin sites.,去极化,肌浆网,刺激,大范围的,传播,Passage of an action potential along the transverse tubule opens nearby voltage-gated calcium channels, the ryanodine receptor l

13、ocated 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.,Which of these

14、 following proteins contains the binding sites for Ca2+ that initiates contraction? A Myosin B Troponin I C Tropomyosin D Troponin C E Troponin T,Neuromuscular transmission Excitation-contraction coupling Muscle contraction,General process of excitation and contraction in skeletal muscle,A single mo

15、tor unit（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）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

16、into the neuromuscular junction.,Muscle contraction follows the delivery of acetylcholine to the muscle fiber.,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 r

17、eceptors 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.,Nicotinic acetylchol

18、ine receptor 烟碱型乙酰胆碱受体,Acetylcholinesterase 乙酰胆碱酯酶,End plate potential (EPP) 终板电位,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 stimulatio

19、n 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.,A woman comes to your clinic and exp

20、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

21、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 blockers,A woman comes to your clinic and explains that she is noting

22、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 weakness of eyelid closure bi

23、laterally. 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 blockers,Neuromuscular transmission A Is caused by the release of acetylcholine from the muscle

24、 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 solely an electronic fu

25、nction,Neuromuscular 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 blocked by curare because i

26、t competes with the Na+ entry during the muscle action potential E Is solely an electronic function,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 f

27、or 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 for weak muscular con

28、tractions 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 nerve ending E Diffusio

29、n into the surrounding extracellular fluid,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 nerve ending E Diffusion into the surrou

30、nding extracellular fluid,The 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 Contraction Coupling C Mem

31、brane Potential D All-or -Nothing Law,The 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 Contraction Co

32、upling C Membrane Potential D All-or -Nothing Law,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 leng

33、th) Isotonic contraction 等张收缩 the muscle shortens while the load on the muscle remains constant (constant tension),Mechanics of single-fiber contraction,The mechanical response of a single muscle fiber to a single action potential is know as a TWITCH,Twitch contraction 单收缩,Tension increases rapidly

34、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,All three are isotonic contractions.,Latent period潜伏期 Velocity of shortening Duration of the twitch Distance sho

35、rtened,Load-velocity relation 长度-速度关系,Answer 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 E,Answer the following question by referring to the attached chart. Which curve or l

36、ine represents the total tension of the muscle? A Curve A B Curve B C Curve C D Curve D E Curve E,Complete dissipation of elastic tension between subsequent stimuli.,S3 occurred prior to the complete dissipation of elastic tension from S2.,S3 occurred prior tothe dissipation of ANY elastic tension f

37、rom S2.,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.,Frequency-tension relation,Mechanism for greater tetanic tension Successive action potentials result in a persistent elevation of cytosolic calcium concentration,Long sarcomere: actin and myosin do not overlap much, so litt

38、le 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,In skeletal muscle, repetitive stimulation leads to fatigue

39、疲劳, evident as reduced tension.,Rest overcomes fatigue, but fatigue will reoccur sooner if inadequate recovery time passes.,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 ATPas

40、e 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

41、 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,Slow-oxidative fibers combine low myosin-ATPase activity with high oxidative capacity Fast-oxidative fibers - combine high m

42、yosin-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,Slow-oxidative skeletal muscle responds well to repetitive stimulation without becoming f

43、atigued; 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

44、 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 IIA fibers are called A Red muscles B Slow oxidative muscles

45、 C White muscles D Fast glycolytic muscles,Muscles containing many type IIA fibers are called A Red muscles B Slow oxidative muscles C White muscles D Fast glycolytic muscles,The store of glycogen in the muscle functions to A Attenuate blood glucose levels directly B Provide energy for muscle contra

46、ction C Provide a source of ketone bodies D Provide structural integrity to muscle E Inhibit muscle contraction,The store of glycogen in the muscle functions to A Attenuate blood glucose levels directly B Provide energy for muscle contraction C Provide a source of ketone bodies D Provide structural

47、integrity to muscle E Inhibit muscle contraction,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 contracti

48、on,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.,Duchenne muscular dystrophy is a devastating, progressive disease that occurs in boys; it is characterized by the progres

49、sive necrosis 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 c

50、ontractures. 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 necrosis and phag