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Skeletal Muscle Physiology（骨骼肌生理）

Huawei Liang, PhDEmail: hwliang@zju.edu.cn

Structure of skeletal muscle

（肌束）

（肌纤维）

Skeletal muscles typically contain many, many muscle fibers.

( 肌原纤维 )

( 肌节 )

( 肌纤维 )

The sarcomere（肌节）is composed of thick filaments（粗肌丝）called myosin（肌球蛋白）, anchored in place by titin fibers, and

thin filaments（细肌丝）called actin（肌动蛋白）, anchored to Z-lines .

A cross section through a sarcomere shows that:• each myosin can interact with 6 actin filaments, and• each actin can interact with 3 myosin filaments.

Sarcomere structures in an electron micrograph.

Filaments

Myosin filament (thick filament)

• Myosin（肌球蛋白）

横桥

Actin filament (thin filament)

• Actin（肌动蛋白）

• Tropomyosin（原肌球蛋白）

• Troponin（肌钙蛋白）

Titin（肌联蛋白）

肌联蛋白源自M线，并沿肌球蛋白纤维伸展，通过肌节的A带，最后到达Z线。

肌联蛋白是高度弹性的分子，因此在肌收缩和舒张时保持肌球蛋白纤维位于肌节的中心。

Sarcotubular system（肌管系统）

(1) Transverse Tubule 横管

(2) Longitudinal Tubule 纵管

Sarcoplasmic reticulum肌浆网

（三联管）

Molecular mechanisms of contraction（收缩）

Sliding-filament mechanism 肌丝滑行机制

Contraction:myosin binds to actin, and slides it, pulling the Z-lines closer together, and reducing the width of the I-bands. Note that filament lengths have not changed.

Contraction: myosin’s cross-bridges bind to actin;the cross-bridges then flex to slide actin.

Click here to play theSarcomere Shortening

Flash Animation

The thick filament called myosin is actually a polymer of myosin molecules, each of which has a flexible cross-bridge that binds ATP and actin.

The cross-bridge cyclerequires ATP

The myosin-binding site on actinbecomes available, so the energized cross-bridge binds.

1.

The full hydrolysis and departure of ADP + Picauses the flexing of the bound 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 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 tropomyosin away from the cross-bridge binding site.

Roles of troponin (肌钙

蛋白), tropomyosin (原肌

球蛋白), and calcium in contraction

Excitation-contraction coupling骨骼肌的兴奋-收缩耦联

• Transmission of action potential (AP) along T tubules

• Calcium release caused by T tubule AP

• Contraction initiated by calcium ions

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 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 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 sarcoplasmicreticulum, andcalcium ions released into the cytosol bind to troponin.The calcium-troponincomplex “pulls” tropomyosinoff the myosin-binding site of actin, thus allowing the binding of the cross-bridge, followed by its flexing to slide the actin filament.

Removal of intracellular calcium ions

• Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA)

• Calsequestrin 钙扣压素

Regulation of SERCA by phospholamban (受磷蛋白)

• Dephosphorylated state: phospholamban inhibits the activity of SERCA by decreasing its affinity for Ca2+

• Phosphorylated state: phospholamban enhances the activity of SERCA by increasing its affinity for Ca2+

General process of excitation and contraction in skeletal muscle

骨骼肌兴奋收缩的基本过程

• Neuromuscular transmission

• Excitation-contraction coupling

• Muscle contraction

A single motor unit consists ofa motor neuron and all of the muscle fibers it controls.

The neuromuscular junction(神经-肌肉接头) is the point of synaptic contactbetween theaxon terminal of a motor neuron and the muscle fiber it controls.

Action potentials in themotor neuron cause Acetylcholine (乙酰胆碱) release into the neuromuscular junction.

Muscle contraction follows the delivery of acetylcholine to the muscle fiber.

1. The exocytosis (出胞) 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 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.

End plate potential (EPP) 终板电位

Click here to play theNeuromuscular Junction

Flash Animation

Click here to play theAction Potentials andMuscle Contraction

Flash Animation

Factors of affecting contractile performance of skeletal muscle

• Preload 前负荷

• Afterload 后负荷

• Contractility 肌肉的收缩能力

Two basic types of contraction

• Isometric contraction 等长收缩: a muscle develops tension but does not shorten (or lengthen) (at a constant length)

• Isotonic contraction 等张收缩: the muscle shortens while the load on the muscle remains constant (at a constant tension)

Tension increases rapidly 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

• Parameters to evaluate contractile performance– Force– Shortening– Duration– Velocity

Long sarcomere:actin and myosindo not overlapmuch, so little tension can bedeveloped.

Length-tension relation

Short sarcomere:actin filamentslack room toslide, so littletension can bedeveloped.

Optimal-length sarcomere:lots of actin-myosin overlapand plenty of room to slide.

Effect of Preload (initial length 初长度)

Load-velocity relation

Effect of Afterload

Effect of Contractility

Summation of Contraction

• Twitch 单收缩

• Tetanus 强直收缩

– Incomplete Tetanus– Complete Tetanus

Frequency-tension relation

Mechanism for greater tetanictension

Successive action potentials result in a persistent elevation of cytosolic calcium concentration

Summary

• Terms– End plate potential– Cross-bridge– Excitation-contraction coupling–– Active tensionActive tension– Isometric contraction & Isotonic contraction

• Describe the molecular mechanisms of muscle contraction

• List the important factors that affect contractile performance of skeletal muscle

Genernal Questions

• How does the relationship of actin and myosin explain the length-tension curve of skeletal muscle?

• “Muscle is a machine for converting chemical into mechanical energy.” Analyze and discuss this statement.

The End.