Skeletal Muscle Physiology
（骨骼肌生理）
Huawei Liang, PhD
Email: hwliang@zju.edu.cn
Structure of skeletal muscle
（肌纤维）
（肌束）
( 肌纤维 )
( 肌原纤维 )
( 肌节 )
Skeletal muscles
typically contain
many, many muscle
fibers.
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 the
Sarcomere 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 cycle
requires ATP
1. The myosin-binding site on actin
becomes available, so the
energized cross-bridge binds.
2.
4. Partial
hydrolysis of
the bound ATP
energizes
or “re-cocks”
the bridge.
3.
The full
hydrolysis
and departure
of ADP + Pi
causes the
flexing of
the bound
cross-bridge.
Binding of a “new” ATP
to the cross-bridge
uncouples the bridge.
Click here to play the
Cross-bridge cycle
Flash Animation
Roles of troponin (肌钙
蛋白), tropomyosin (原肌
球蛋白), and calcium in
contraction
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.
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 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.
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
potential 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 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 of
a 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 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 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 terminal
occurs when the acetylcholine 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 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 the
Neuromuscular Junction
Flash Animation
Click here to play the
Action Potentials and
Muscle 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)
iso = same
tonic = tension
metric = length
Tension increases
rapidly and
dissipates slowly
Shortening occurs
slowly, only after
taking up elastic
tension; the
relaxing muscle
quickly returns to
its resting length.
• Parameters to evaluate contractile performance
–
–
–
–
Force
Shortening
Duration
Velocity
Effect of Preload (initial
length 初长度)
Short sarcomere:
actin filaments
lack room to
slide, so little
tension can be
developed.
Length-tension relation
Optimal-length sarcomere:
lots of actin-myosin overlap
and plenty of room to slide.
Long sarcomere:
actin and myosin
do not overlap
much, so little
tension can be
developed.
Effect of Afterload
Load-velocity relation
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 tetanic
tension
Successive action
potentials result in a
persistent elevation of
cytosolic calcium
concentration
Summary
• Terms
–
–
–
–
–
End plate potential
Cross-bridge
Excitation-contraction coupling
Active 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.