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1、Skeletal Muscle 骨骼肌,Types of muscle: Skeletal muscle骨骼肌 Cardiac muscle 心肌 Smooth muscle平滑肌,Striated muscle 橫紋肌,Muscle,Muscle (cont.),The sliding filament mechanism(肌絲滑行機(jī)制), in which myosin(肌凝蛋白) filaments bind to and move actin (肌纖蛋白)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
3、 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 muscle,Skeletal muscles are attached t
4、o the skeleton by tendons.,Skeletal muscles typically contain many, many muscle fibers.,The sarcomere(肌小節(jié)) 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 that: each myo
5、sin can interact with 6 actin filaments, and each actin can interact with 3 myosin filaments.,Sarcomere structures in an electron micrograph.,Filaments,Myosin肌凝蛋白,Myosin filament (thick filament)粗肌絲,Actin肌纖蛋白 Tropomyosin原肌凝蛋白 Troponin肌鈣蛋白,Actin filament (thin filament)細(xì)肌絲,Titin肌聯(lián)蛋白,Sarcotubular syst
6、em,(1) Transverse Tubule橫管 (2) Longitudinal Tubule縱管 Sarcoplasmic reticulum肌漿網(wǎng),Molecular mechanisms of contraction,Sliding-filament mechanism,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
7、 lengths have not changed.,Contraction: myosins cross-bridges(橫橋) bind to actin; the crossbridges then flex to slide actin.,Click here to play the Sarcomere Shortening Flash Animation,The thick filament called myosin is actually a polymer of myosin molecules, each of which has a flexible cross-bridg
8、e that binds ATP and actin.,The cross-bridge cycle requires ATP,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.,The cross-bridge cycle requires ATP,The myosin-bindi
9、ng site on actin becomes available, so the energized cross-bridge binds.,1.,Click here to play the Cross-bridge cycle Flash Animation,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
10、tropomyosin away from the cross-bridge binding site.,Roles of troponin, tropomyosin, and calcium in contraction,Interaction of myosin and actin,Transmission of action potential (AP) along T tubules Calcium release caused by T tubule AP Contraction initiated by calcium ions,Excitation-contraction cou
11、pling 興奮-收縮偶聯(lián),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.,The transverse tubules bring action potentials into the interior of the skeletal musc
12、le 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.,Passage of an action p
13、otential 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
14、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 Troponin C E Troponin T,Neuromuscular transmission Excitation-contrac
15、tion coupling Muscle contraction,General process of excitation and contraction in skeletal muscle,A single motor unit(運(yùn)動(dòng)單位) consists of a motor neuron and all of the muscle fibers it controls.,The neuromuscular junction(神經(jīng)肌接頭)is the point of synaptic contact between the axon terminal of a motor neur
16、on and the muscle fiber it controls.,Action potentials in the motor neuron cause Acetylcholine(乙酰膽堿) release 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 acetyl
17、choline 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 nea
18、rby voltage-gate Na+ and K+ channels, so an action potential occurs on the muscle fiber.,Nicotinic acetylcholine receptor 煙堿型乙酰膽堿受體,Acetylcholinesterase 乙酰膽堿酯酶,End plate potential (EPP) 終板電位,Miniature end plate potential 微終板電位 Small fluctuations (typically 0.5 mV) in the resting potential of postsyn
19、aptic 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
20、resulting from the release of the contents of a single synaptic vesicle.,Click here to play the Neuromuscular Junction Flash Animation,Click here to play the Action Potentials and Muscle Contraction Flash Animation,A woman comes to your clinic and explains that she is noting gradually worsening fati
21、gue/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 bilaterally. The rest of t
22、he 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 gradually worsening fatigue/weakness in her legs
23、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 bilaterally. The rest of the exam is unremarkable.
24、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 side of the junction B Shows a permeability chan
25、ge 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 function,Neuromuscular transmission A Is caused by
26、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 it competes with the Na+ entry during the muscle a
27、ction 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 for weak muscular contractions E An afterdischarge
28、 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 contractions E An afterdischarge at the neuromuscula
29、r 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 Diffusion into the surrounding extracellular fluid,The ac
30、tion 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 surrounding extracellular fluid,The transmission of an
31、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 Membrane Potential D All-or -Nothing Law,The transmi
32、ssion 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 Membrane Potential D All-or -Nothing Law
33、,Muscle tension 肌張力 the force exerted on an object by a contracting muscle Load 負(fù)荷 the force exerted on the muscle by an object (usually its weight) Isometric contraction 等長(zhǎng)收縮 a muscle develops tension but does not shorten (or lengthen) (constant length) Isotonic contraction 等張收縮 the muscle shortens
34、 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 單收縮,Tension increases rapidly and dissipates slowly,Shortening occurs slowly, o
35、nly 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潛伏期 Velocity of shortening Duration of the twitch Distance shortened,Load-velocity relation 長(zhǎng)度-速度關(guān)系,Click here
36、to play the Mechanisms of Single Fiber Contraction Flash Animation,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 att
37、ached 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,Complete dissipation of elastic tension between subsequent stimuli.,S3 occurred prior to the complete dissipation of elastic tension from S2.,S3 occurred prior tothe dissipa
38、tion of ANY elastic tension from S2.,Frequency-tension relation頻率-張力關(guān)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
39、 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,Click here to play the Length-
40、Tension Relation in Skeletal Muscles Flash Animation,In skeletal muscle, repetitive stimulation leads to fatigue疲勞, 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快肌纖維
41、 containing myosin with high ATPase activity (type II fibers) Slow fibers慢肌纖維 - containing myosin with low ATPase activity (type I fibers) On the basis of major pathway to form ATP Oxidative fibers氧化型肌纖維 containing numerous mitochondria and having a high capacity for oxidative phosphorylation, also
42、containing large amounts of myoglobin (red muscle fibers) Glycolytic fibers糖酵解型肌纖維 - 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,Slow-oxidati
43、ve 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
44、skeletal muscle fibers,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
45、.,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.,Note: Because fast-glycolytic fibers have significant glycolytic capacity, they are sometimes called “fast oxidative-
46、glycolytic FOG fibers.,Muscles containing many type IIA fibers are called A Red muscles B Slow oxidative muscles 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
47、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 integrity to muscle E Inhibit muscle contraction,The store of glycogen in the muscle functions to A Attenuate blood glucose l
48、evels directly B Provide energy for muscle contraction C Provide a source of ketone bodies D Provide structural 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 contribut
49、ions to the development of muscle tension.,Slow-oxidative,Fast-oxidative,Fast- glycolytic,Whole-muscle contraction,Flexors(屈?。゛nd extensors(伸?。?work in antagonistic sets to refine movement, and to allow force generation in two opposite directions.,How can gastrocnemius contraction result in two diff
50、erent movements?,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.,Muscle contraction that moves the attachment site on bone 1 cm results in a 7 cm movement of the object 30 cm away
51、from the site; similar gains in movement velocity occur.,Duchenne muscular dystrophy(Duchenne型肌營(yíng)養(yǎng)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 t
52、hat occurs in boys; it is characterized by the progressive 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 contractures. 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 sarcopla
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