Skeletal Muscle

• Each muscle is served by one artery, one

nerve, and one or more veins

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 Skeletal Muscle

• Connective tissue sheaths of skeletal muscle:

• Epimysium: dense regular connective tissue
surrounding entire muscle
• Perimysium: fibrous connective tissue surrounding
fascicles (groups of muscle fibers)
• Endomysium: fine areolar connective tissue
surrounding each muscle fiber

Copyright © 2010 Pearson Education, Inc.

 Epimysium

Bone Epimysium Perimysium

Tendon Endomysium
Muscle fiber
in middle of
a fascicle
(b) Blood vessel
Fascicle
(wrapped by perimysium)
Endomysium
(between individual
muscle fibers)

Perimysium Fascicle Muscle fiber

(a)

Copyright © 2010 Pearson Education, Inc. Figure 9.1

 Skeletal Muscle: Attachments

• Muscles attach:
• Directly—epimysium of muscle is fused to the
periosteum of bone or perichondrium of
cartilage
• Indirectly—connective tissue wrappings extend
beyond the muscle as a ropelike tendon or
sheetlike aponeurosis

Copyright © 2010 Pearson Education, Inc.

Copyright © 2010 Pearson Education, Inc. Table 9.1
 Microscopic Anatomy of a Skeletal Muscle
Fiber
• Cylindrical cell 10 to 100 m in diameter, up
to 30 cm long
• Multiple peripheral nuclei
• Many mitochondria
• Glycosomes for glycogen storage, myoglobin
for O2 storage
• Also contain myofibrils, sarcoplasmic
reticulum, and T tubules

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 Myofibrils

• Densely packed, rodlike elements

• ~80% of cell volume
• Exhibit striations: perfectly aligned repeating
series of dark A bands and light I bands

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 Sarcolemma

Mitochondrion

Myofibril

Dark A band Light I band Nucleus

(b) Diagram of part of a muscle fiber showing the myofibrils. One
myofibril is extended afrom the cut end of the fiber.

Copyright © 2010 Pearson Education, Inc.

 Sarcomere

• Smallest contractile unit (functional unit) of a

muscle fiber
• The region of a myofibril between two
successive Z discs
• Composed of thick and thin myofilaments
made of contractile proteins

Copyright © 2010 Pearson Education, Inc.

 Features of a Sarcomere

• Thick filaments: run the entire length of an A band

• Thin filaments: run the length of the I band and
partway into the A band
• Z disc: coin-shaped sheet of proteins that anchors
the thin filaments and connects myofibrils to one
another
• H zone: lighter midregion where filaments do not
overlap
• M line: line of protein myomesin that holds adjacent
thick filaments together

Copyright © 2010 Pearson Education, Inc.

 Thin (actin)
filament Z disc H zone Z disc

Thick (myosin) I band A band I band M line

filament Sarcomere
(c) Small part of one myofibril enlarged to show the myofilaments
responsible for the banding pattern. Each sarcomere extends from
one Z disc to the next.

Sarcomere
Z disc M line Z disc
Thin (actin)
filament
Elastic (titin)
filaments
Thick
(myosin)
filament

(d) Enlargement of one sarcomere (sectioned lengthwise). Notice the

myosin heads on the thick filaments.

Copyright © 2010 Pearson Education, Inc. Figure 9.2c, d

 Ultrastructure of Thick Filament

• Composed of the protein myosin

• Myosin tails contain:
• 2 interwoven, heavy polypeptide chains
• Myosin heads contain:
• 2 smaller, light polypeptide chains that act as cross
bridges during contraction
• Binding sites for actin of thin filaments
• Binding sites for ATP
• ATPase enzymes

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 Ultrastructure of Thin Filament

• Twisted double strand of fibrous protein F

actin
• F actin consists of G (globular) actin subunits
• G actin bears active sites for myosin head
attachment during contraction
• Tropomyosin and troponin: regulatory proteins
bound to actin

Copyright © 2010 Pearson Education, Inc.

 Longitudinal section of filaments
within one sarcomere of a myofibril

Thick filament
Thin filament
In the center of the sarcomere, the thick
filaments lack myosin heads. Myosin heads
are present only in areas of myosin-actin overlap.
Thick filament Thin filament
Each thick filament consists of many A thin filament consists of two strands
myosin molecules whose heads protrude of actin subunits twisted into a helix
at opposite ends of the filament. plus two types of regulatory proteins
(troponin and tropomyosin).
Portion of a thick filament
Myosin head Portion of a thin filament
Tropomyosin Troponin Actin

Actin-binding sites
Heads Tail Active sites
ATP- Actin for myosin
binding Flexible hinge region subunits attachment
site
Myosin molecule Actin subunits

Copyright © 2010 Pearson Education, Inc. Figure 9.3

 Sarcoplasmic Reticulum (SR)

• Network of smooth endoplasmic reticulum

surrounding each myofibril
• Pairs of terminal cisternae form perpendicular
cross channels
• Functions in the regulation of intracellular Ca2+
levels

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 T Tubules

• Continuous with the sarcolemma

• Penetrate the cell’s interior at each A band–I
band junction
• Associate with the paired terminal cisternae to
form triads that encircle each sarcomere

Copyright © 2010 Pearson Education, Inc.

 Part of a skeletal
muscle fiber (cell) I band A band I band
Z disc H zone Z disc
Myofibril M line

Sarcolemma
Triad:
• T tubule
• Terminal
Sarcolemma cisternae
of the SR (2)
Tubules of
the SR
Myofibrils
Mitochondria

Copyright © 2010 Pearson Education, Inc. Figure 9.5

 Triad Relationships

• T tubules conduct impulses deep into muscle

fiber
• Integral proteins protrude into the
intermembrane space from T tubule and SR
cisternae membranes
• T tubule proteins: voltage sensors
• SR foot proteins: gated channels that regulate
Ca2+ release from the SR cisternae

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 Contraction

• The generation of force

• Does not necessarily cause shortening of the
fiber
• Shortening occurs when tension generated by
cross bridges on the thin filaments exceeds
forces opposing shortening

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 Sliding Filament Model of Contraction

• In the relaxed state, thin and thick filaments

overlap only slightly
• During contraction, myosin heads bind to
actin, detach, and bind again, to propel the
thin filaments toward the M line
• As H zones shorten and disappear,
sarcomeres shorten, muscle cells shorten,
and the whole muscle shortens

Copyright © 2010 Pearson Education, Inc.

 Z H Z
I A I
1 Fully relaxed sarcomere of a muscle fiber

Z Z
I A I
2 Fully contracted sarcomere of a muscle fiber
Copyright © 2010 Pearson Education, Inc. Figure 9.6
 Requirements for Skeletal Muscle
Contraction
1. Activation: neural stimulation at a
neuromuscular junction
2. Excitation-contraction coupling:
• Generation and propagation of an action
potential along the sarcolemma
• Final trigger: a brief rise in intracellular Ca2+
levels

Copyright © 2010 Pearson Education, Inc.

 Events at the Neuromuscular Junction

• Skeletal muscles are stimulated by somatic

motor neurons
• Axons of motor neurons travel from the
central nervous system via nerves to skeletal
muscles
• Each axon forms several branches as it
enters a muscle
• Each axon ending forms a neuromuscular
junction with a single muscle fiber

Copyright © 2010 Pearson Education, Inc.

 Myelinated axon
Action
of motor neuron
potential (AP)
Axon terminal of
Nucleus neuromuscular
junction
Sarcolemma of
the muscle fiber

1 Action potential arrives at

axon terminal of motor neuron.
Ca2+ Synaptic vesicle
Ca2+
2 Voltage-gated Ca2+ channels containing ACh
open and Ca2+ enters the axon Mitochondrion
terminal. Synaptic
Axon terminal
of motor neuron cleft

Fusing synaptic
vesicles

Copyright © 2010 Pearson Education, Inc. Figure 9.8

 Neuromuscular Junction

• Situated midway along the length of a muscle

fiber
• Axon terminal and muscle fiber are separated
by a gel-filled space called the synaptic cleft
• Synaptic vesicles of axon terminal contain the
neurotransmitter acetylcholine (ACh)
• Junctional folds of the sarcolemma contain
ACh receptors

Copyright © 2010 Pearson Education, Inc.

 Events at the Neuromuscular Junction

• Nerve impulse arrives at axon terminal

• ACh is released and binds with receptors on
the sarcolemma
• Electrical events lead to the generation of an
action potential

PLAY A&P Flix™: Events at the Neuromuscular Junction

Copyright © 2010 Pearson Education, Inc.

 Myelinated axon
Action
of motor neuron
potential (AP)
Axon terminal of
Nucleus neuromuscular
junction
Sarcolemma of
the muscle fiber

1 Action potential arrives at

axon terminal of motor neuron.
Ca2+ Synaptic vesicle
Ca2+
2 Voltage-gated Ca channels
2+ containing ACh
open and Ca2+ enters the axon Mitochondrion
terminal. Axon terminal Synaptic
of motor neuron
cleft
3 Ca2+ entry causes some Fusing synaptic
synaptic vesicles to release vesicles

their contents (acetylcholine) Junctional

by exocytosis. ACh folds of
sarcolemma
4 Acetylcholine, a
neurotransmitter, diffuses across Sarcoplasm of
the synaptic cleft and binds to muscle fiber
receptors in the sarcolemma.
5 ACh binding opens ion Na+ K+ Postsynaptic membrane
channels that allow simultaneous ion channel opens;
passage of Na+ into the muscle ions pass.
fiber and K+ out of the muscle
fiber.

6 ACh effects are terminated Ach– Degraded ACh

Postsynaptic membrane
Na+
by its enzymatic breakdown in ion channel closed;
the synaptic cleft by ions cannot pass.
acetylcholinesterase. Acetyl-
cholinesterase
K+

Copyright © 2010 Pearson Education, Inc. Figure 9.8

 Destruction of Acetylcholine

• ACh effects are quickly terminated by the

enzyme acetylcholinesterase
• Prevents continued muscle fiber contraction in
the absence of additional stimulation

Copyright © 2010 Pearson Education, Inc.

 Events in Generation of an Action Potential

1. Local depolarization (end plate potential):

• ACh binding opens chemically (ligand)
gated ion channels
• Simultaneous diffusion of Na+ (inward) and
K+ (outward)
• More Na+ diffuses, so the interior of the
sarcolemma becomes less negative
• Local depolarization – end plate potential

Copyright © 2010 Pearson Education, Inc.

 Events in Generation of an Action Potential

2. Generation and propagation of an action

potential:
• End plate potential spreads to adjacent
membrane areas
• Voltage-gated Na+ channels open
• Na+ influx decreases the membrane voltage
toward a critical threshold
• If threshold is reached, an action potential is
generated

Copyright © 2010 Pearson Education, Inc.

 Events in Generation of an Action Potential

• Local depolarization wave continues to

spread, changing the permeability of the
sarcolemma
• Voltage-regulated Na+ channels open in the
adjacent patch, causing it to depolarize to
threshold

Copyright © 2010 Pearson Education, Inc.

 Events in Generation of an Action Potential

3. Repolarization:
• Na+ channels close and voltage-gated K+
channels open
• K+ efflux rapidly restores the resting polarity
• Fiber cannot be stimulated and is in a
refractory period until repolarization is
complete
• Ionic conditions of the resting state are
restored by the Na+-K+ pump

Copyright © 2010 Pearson Education, Inc.

 Axon terminal
Open Na+ Closed K+
Channel Channel
Synaptic Na+
cleft

ACh
Na+ K+ K+
++ +
ACh ++ + Action potential + +++
+ +

n
Na+ K+
tio
2 Generation and propagation of
i za
l ar
the action potential (AP)
po
de
of

e
Wa v Closed Na+ Open K+
Channel Channel
1 Local depolarization: Na+
generation of the end
plate potential on the
sarcolemma
K+
Sarcoplasm of muscle fiber 3 Repolarization

Copyright © 2010 Pearson Education, Inc. Figure 9.9

 Axon terminal

Open Na+ Closed K+

Channel Channel
Synaptic Na+
cleft

ACh
K+
Na +
K
+ ++ +
+ +++
ACh io
n ++ +
+
Action potential
+
Na+ K+
t
iza
l ar
d ep o
of

ve
Wa

1 Local depolarization: generation of the

end plate potential on the sarcolemma
Sarcoplasm of muscle fiber

Copyright © 2010 Pearson Education, Inc. Figure 9.9, step 1

 Axon terminal

Open Na+ Closed K+

Channel Channel
Synaptic Na+
cleft

ACh
K+
Na +
K
+ ++ +
+ +++
ACh io
n ++ +
+
Action potential
+
Na+ K+
t
iza

2 Generation and propagation of the

l ar

action potential (AP)

d ep o
of

ve
Wa

1 Local depolarization: generation of the

end plate potential on the sarcolemma
Sarcoplasm of muscle fiber

Copyright © 2010 Pearson Education, Inc. Figure 9.9, step 2

 Closed Na+ Open K+
Channel Channel
Na+

K+
3 Repolarization

Copyright © 2010 Pearson Education, Inc. Figure 9.9, step 3

 Axon terminal
Open Na+ Closed K+
Channel Channel
Synaptic Na+
cleft

ACh
Na+ K+ K+
++ +
ACh ++ + Action potential + +++
+ +

n
Na+ K+
tio
2 Generation and propagation of
i za
l ar
the action potential (AP)
po
de
of

e
Wa v Closed Na+ Open K+
1 Local depolarization: Channel Channel
Na+
generation of the end
plate potential on the
sarcolemma
K+
Sarcoplasm of muscle fiber 3 Repolarization

Copyright © 2010 Pearson Education, Inc. Figure 9.9

 Na+ channels
close, K+ channels
Depolarization open
due to Na+ entry

Repolarization
due to K+ exit
Na+
channels
open
Threshold

K+ channels
close

Copyright © 2010 Pearson Education, Inc. Figure 9.10

 Excitation-Contraction (E-C) Coupling

• Sequence of events by which transmission of

an AP along the sarcolemma leads to sliding
of the myofilaments
• Latent period:
• Time when E-C coupling events occur
• Time between AP initiation and the beginning
of contraction

Copyright © 2010 Pearson Education, Inc.

 Events of Excitation-Contraction (E-C)
Coupling
• AP is propagated along sarcomere to T
tubules
• Voltage-sensitive proteins stimulate Ca2+
release from SR
• Ca2+ is necessary for contraction

Copyright © 2010 Pearson Education, Inc.

 Setting the stage

Axon terminal
of motor neuron
Synaptic cleft Action potential
is generated
ACh Sarcolemma
Terminal cisterna of SR

Muscle fiber Ca2+

Triad

One sarcomere

Copyright © 2010 Pearson Education, Inc. Figure 9.11, step 1

 Steps in E-C Coupling:

Sarcolemma
Voltage-sensitive T tubule
tubule protein 1 Action potential is propagated along
the sarcolemma and down the T tubules.

Ca2+
release
channel
2 Calcium ions are released.
Terminal
cisterna
of SR

Ca2+

Actin

Troponin Tropomyosin
Ca2+ blocking active sites

Myosin

3 Calcium binds to troponin and

removes the blocking action of
tropomyosin.

Active sites exposed and

ready for myosin binding

4 Contraction begins
Myosin
cross
bridge

The aftermath

Copyright © 2010 Pearson Education, Inc. Figure 9.11, step 2

 1 Action potential is
propagated along the
sarcolemma and down
Steps in the T tubules.
E-C Coupling:
Sarcolemma
Voltage-sensitive T tubule
tubule protein

Ca2+
release
channel
Terminal
cisterna
of SR

Ca2+

Copyright © 2010 Pearson Education, Inc. Figure 9.11, step 3

 1 Action potential is
propagated along the
sarcolemma and down
Steps in the T tubules.
E-C Coupling:
Sarcolemma
Voltage-sensitive T tubule
tubule protein

Ca2+
release
channel 2 Calcium
ions are
Terminal released.
cisterna
of SR

Ca2+

Copyright © 2010 Pearson Education, Inc. Figure 9.11, step 4

 Actin
Troponin Tropomyosin
Ca2+ blocking active sites
Myosin

The aftermath

Copyright © 2010 Pearson Education, Inc. Figure 9.11, step 5

 Actin
Troponin Tropomyosin
Ca2+ blocking active sites
Myosin
3 Calcium binds to
troponin and removes
the blocking action of
tropomyosin.
Active sites exposed and
ready for myosin binding

The aftermath

Copyright © 2010 Pearson Education, Inc. Figure 9.11, step 6

 Actin
Troponin Tropomyosin
Ca2+ blocking active sites
Myosin
3 Calcium binds to
troponin and removes
the blocking action of
tropomyosin.
Active sites exposed and
ready for myosin binding

4 Contraction begins
Myosin
cross
bridge
The aftermath

Copyright © 2010 Pearson Education, Inc. Figure 9.11, step 7

 Steps in E-C Coupling:

Sarcolemma
Voltage-sensitive T tubule
tubule protein 1 Action potential is propagated along
the sarcolemma and down the T tubules.

Ca2+
release
channel
2 Calcium ions are released.
Terminal
cisterna
of SR

Ca2+

Actin

Troponin Tropomyosin
Ca2+ blocking active sites

Myosin

3 Calcium binds to troponin and

removes the blocking action of
tropomyosin.

Active sites exposed and

ready for myosin binding

4 Contraction begins
Myosin
cross
bridge

The aftermath

Copyright © 2010 Pearson Education, Inc. Figure 9.11, step 8

 Role of Calcium (Ca2+) in Contraction

• At low intracellular Ca2+ concentration:

• Tropomyosin blocks the active sites on actin
• Myosin heads cannot attach to actin
• Muscle fiber relaxes

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 Role of Calcium (Ca2+) in Contraction

• At higher intracellular Ca2+ concentrations:

• Ca2+ binds to troponin
• Troponin changes shape and moves
tropomyosin away from active sites
• Events of the cross bridge cycle occur
• When nervous stimulation ceases, Ca2+ is
pumped back into the SR and contraction ends

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 Cross Bridge Cycle

• Continues as long as the Ca2+ signal and

adequate ATP are present
• Cross bridge formation—high-energy myosin
head attaches to thin filament
• Working (power) stroke—myosin head pivots
and pulls thin filament toward M line

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 Cross Bridge Cycle

• Cross bridge detachment—ATP attaches to

myosin head and the cross bridge detaches
• “Cocking” of the myosin head—energy from
hydrolysis of ATP cocks the myosin head into
the high-energy state

Copyright © 2010 Pearson Education, Inc.

 Thin filament
Actin Ca 2+

ADP
Myosin Pi
cross bridge

Thick
filament
Myosin
1 Cross bridge formation.

ADP
ADP
Pi ATP Pi
hydrolysis

4 Cocking of myosin head. 2 The power (working)

stroke.

ATP

ATP

3 Cross bridge
detachment.

Copyright © 2010 Pearson Education, Inc. Figure 9.12

 Actin Ca2+ Thin filament

ADP
Myosin
Pi
cross bridge
Thick filament

Myosin

1 Cross bridge formation.

Copyright © 2010 Pearson Education, Inc. Figure 9.12, step 1

 ADP
Pi

2 The power (working) stroke.

Copyright © 2010 Pearson Education, Inc. Figure 9.12, step 3

 ATP

3 Cross bridge detachment.

Copyright © 2010 Pearson Education, Inc. Figure 9.12, step 4

 ADP
Pi ATP
hydrolysis

4 Cocking of myosin head.

Copyright © 2010 Pearson Education, Inc. Figure 9.12, step 5

 Thin filament
Actin Ca 2+

ADP
Myosin Pi
cross bridge

Thick
filament
Myosin
1 Cross bridge formation.

ADP
ADP
Pi ATP Pi
hydrolysis

4 Cocking of myosin head. 2 The power (working)

stroke.

ATP

ATP

3 Cross bridge
detachment.

Copyright © 2010 Pearson Education, Inc. Figure 9.12