Overview

Cellular Structure of Muscle

(pp378-385, 407-414)

Mechanism of Muscle Contraction

Neuromuscular Junction
Excitation - Contraction Coupling
Cross Bridge Cycle

Figure 12.1 The three types of muscles

Skeletal muscle fibers are large,

multinucleate cells that appear
striped or striated under the
microscope.

Nucleus

Muscle fiber
(cell)
Striations

Cardiac muscle fibers are also

striated but they are smaller,
branched, and uninucleate.
Cells are joined in series by
junctions called intercalated
disks.

Nucleus
Muscle fiber

Intercalated
disk
Striations

Smooth muscle fibers are small

and lack striations.
Nucleus

Muscle fiber

Characteristic

Smooth

Cardiac

Skeletal

Nuclei

Single nucleus

Single nucleus

Multinucleated

Striated

Non-striated

Striated

Striated

Cellular
Junctions

Some have gap

junctions

Intercalated
discs

No

Muscle fiber
shape

Spindle-shaped

Branched

Cylindrical

Contraction

Involuntary

Involuntary

Voluntary

Figure 12.2 Antagonistic muscles

Flexion moves bones

closer together.

Triceps
muscle
relaxes.

Extension moves bones

away from each other.

Triceps muscle
contracts
(extensor).
Biceps muscle
contracts (flexor).

Antagonistic muscles exert opposite effects.

Biceps
muscle
relaxes.

Muscle Organization
Muscle
fascicle: bundle of
muscle fibers
muscle fiber: a fused
muscle cell

Tendon
Bone
Connective tissues
Endomysium
Perimysium
Epimysium
Vanders Human Physiology, 13

th

edition

Figure 12.3

 Due to its elongated shape and the presence of multiple nuclei, a

skeletal muscle cell is also referred to as a muscle fiber.
Each muscle fiber is sheathed in connective tissue, with groups of
adjacent fibers bundled into muscle fascicles.
Each muscle fiber is formed during development by the fusion of a
number of undifferentiated, mononucleated cells, known as
myoblasts, into a single cylindrical, multinucleated cell.
After muscle damage, new fibers can be formed from undifferentiated
satellite cells located adjacent to the muscle fibers.
http://journal.frontiersin.org/Journal/10.3389/fimmu.2014
.00034/full

Figure 12.3

Figure 12.3b Skeletal Muscles

Structure of a Skeletal Muscle Fiber

Mitochondria
Sarcoplasmic
reticulum
Nucleus

Thick
filament

Thin
filament

T-tubules

Myofibril
Sarcolemma

Transverse tubule (T-tubule) - extension of the membrane

into the muscle cells. Propagates AP deep into the center of
skeletal muscle cells.
Sarcoplasmic reticulum (SR) homologous to endoplasmic
reticulum (ER). Form sleeve-like segments around each myofibril.
Ca2+ storage in muscle cells.

Figure 12.4

Muscle
Structure

Each muscle fiber contains many chains of myofibrils.

The fundamental unit of contraction is sarcomere.
Sarcomeres are normally arranged into bands or lines.
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Skeletal Muscle Characteristics

Diameter 10-100m, length up to 20 cm.
Each nucleus regulates gene expression and protein
synthesis within its local domain.
Myofibrils cylindrical bundles, 1-2m in diameter, rodlike units of a muscle (along the direction of the muscle).
Transverse tubules (T-tubules) the continuation of
cell membrane into the cell, fluid in T-tubule is
continuous with extracellular fluid.
Sarcoplasmic reticulum (SR) a form of modified
endoplasmic reticulum that wraps around each myofibril
and stores Ca2+
Sarcomere unit of contraction in a myofibril
Muscle physiology uses specialized vocabulary:
Sarcolemma = Plasma membrane
Sarcoplasm = Cytoplasm
Sarcoplasmic reticulum = Smooth ER

12

Figure 12.3

13

Structure of Skeletal Muscle

Muscle fiber (single muscle cell)

Myofibril

Sarcomere: the
unit of
contraction in a
myofibril.

A band I band

Z line

Z line

Sarcomere
M line
Z line

Z line

A band / I band
Z line
H zone (M line)

H zone

Thick (myosin) filament

Thin (actin) filament

Vanders Human Physiology, 13th edition

Sliding-Filament Mechanism

15

Figure 12.5de The Sarcomere

The sarcomere shortens during contraction. As contraction takes place, actin

and myosin do not change length but instead slide past one another.

A band

I band

Muscle Relaxed

Myosin
Actin

Sarcomere
shortens with
contraction.

Half of
I band

Half of
I band

H zone

Z line

Muscle Contracted
H zone and I band both
shorten, while A band
remains constant.
I

Myosin binds to actin, and slides on it, pulling the adjacent Zlines closer, and reduces the width of the I-bands and H
bands.
Filament lengths and A bands lengths are not changed.

Summary

A band = myosin fiber length (fixed length)

I band = free actin filament (may shorten)
H zone = free myosin filament (may
shorten)
Z line = anchor of actin filament
M line = anchor of myosin filament
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Other Proteins in Sarcomere

Figure 12.6

Titin is a giant protein, with its length of ~27,000 to ~33,000 amino

acid and greater than 1 m in length, that functions as a molecular
spring which is responsible for the passive elasticity of muscle.
It is believed that nebulin acts as a thin filament "ruler" and
regulates thin filament length during sarcomere assembly. (reference)18

Other Proteins in Sarcomere

Tropomyosin lies within
the groove between
the double row of actin
monomers.
Troponin, a complex of
three proteins, is
attached to the
tropomyosin, rather
than directly to the
actin.
Fox's Human Physiology 12th Edition

19

Overview
Cellular Structure of Muscle
Mechanism of Muscle
Contraction (pp385-391, 415-420)
Neuromuscular Junction
Excitation - Contraction Coupling
Cross Bridge Cycle

20

Figure 5.24

21

Quick
Preview/Review of
Action Potential

22

A single motor unit

consists
of one motor neuron
and all the muscle
fibers it controls.
The synaptic contact
between the axon
terminal
of a motor neuron and
the
muscle fiber it controls
is called a
neuromuscular
junction.

23

24
Figure 12.11

Neuromuscular Junction (NMJ)

Active zone: the presynaptic site of
neurotransmitter
release
End plate: the
postsynaptic folds at
the muscle membrane
Action potentials in the
motor neuron cause
acetylcholine release
into
the neuromuscular
junction.
Muscle contraction

25

3:18 video https://

www.youtube.com/watch?v=7wM5_aUn2qs

26

Figure 12.10

The binding of ACh to nAChR induces a net Na+

influx, which initiates a muscle action potential.

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Neuromuscular Junction
The exocytosis of acetylcholine (ACh) from the
axon terminal occurs when the acetylcholine
vesicles merge into the membrane covering the
terminal.
On the membrane of the muscle fiber, the ACh
receptors (nicotinic cholinergic receptor) respond
to ACh binding by Na+ influx.
If the Na+ influx is large enough, it triggers an
action potential on the muscle fiber.
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Botulinum toxin is a protein and neurotoxin produced by

the bacterium Clostridium botulinum.

Botulinum toxin specifically prevents release of

acetylcholine when injected.

A groups of cosmetic drugs (Botox, Dysport, Myobloc and

Xeomin) include botulinum toxins.
29
Figure from http://www.wmcri.com/botox/

Overview
Cellular Structure of Muscle
Mechanism of Muscle
Contraction (pp385-391, 415-420)
Neuromuscular Junction
Excitation - Contraction Coupling
Cross Bridge Cycle

30

2:13 video https://www.youtube.com/watch?v=HJj3jUVDFFo

31

Figure 12.11

The latent period between excitation and development of tension in a

skeletal muscle includes the time needed to release Ca2+ from
sarcoplasmic reticulum, binding of Ca2+ with troponin, and
initiation of contraction.

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Ca2+ release mechanism in skeletal muscle

DHP receptor voltage sensor located on T-tubules.

(Dihydropyridine, DHP is a blocker of this protein/Ca 2+ channel)

Ryanodine receptor - voltage-gated calcium channel

(Ryanodine is a high affinity toxin that locks the channel in open state)
http://en.wikipedia.org/wiki/Ryanodine

33

Figure 12.8 Troponin and tropomyosin

Relaxed state. Myosin head cocked. Tropomyosin

partially blocks binding site on actin. Myosin is
weakly bound to actin.

Initation of contraction. A calcium signal

initiates contraction.

Ca2 levels increase

in cytosol.

Cytosolic Ca2
Troponin

G-actin

Tropomyosin shifts,
exposing binding
site on actin.

TN

TN
Myosin head

Tropomyosin
Pi

ADP

ADP

Actin
moves

Ca2 binds to
troponin (TN).
Troponin-Ca2
complex pulls
tropomyosin
away from actins
myosin-binding site.

Power stroke
Pi

Myosin binds strongly

to actin and completes
power stroke.

Actin filament
moves.

Troponin - Ca2+
sensing
Tropomyosin blocks the binding
site of myosin on
actin.
Ca2+ binds to specific
binding sites on
troponin and produces
a conformational
change, which moves
tropomyosin away
FYI: The troponin test
from
myosin binding
measures the levels of
troponin
site
onsubunits
actin.troponin T
and troponin I in the blood.
These proteins arereleased
when the heart muscle has

35

Figure 12.10b

36

Overview
Cellular Structure of Muscle
Mechanism of Muscle
Contraction (pp385-391, 415-420)
Neuromuscular Junction
Excitation - Contraction Coupling
Cross Bridge Cycle

37

ATP binding detaches the cross-bridge between actin and myosin

Fox's Human Physiology 12th Edition
38

Figure 12.9-0 The contraction cycle

Tight Binding in the Rigor State
G-actin molecule

Myosin
binding sites

Myosin filament

NAVIGATOR

ATP binds.

ADP
releases.

Myosin releases ADP at the

end of the power stroke.

ATP binds to myosin.

Myosin releases actin.

Contractionrelaxation

Myosin hydrolyzes ATP. Energy

from ATP rotates the myosin head
to the cocked position. Myosin
binds weakly to actin.

The Power Stroke

Actin filament moves toward M line.

Sliding filament

Head
swivels.
Myosin
releases Pi.

Ca2
signal
Power stroke begins
when tropomyosin
(not shown) moves
off the binding site.

ADP
Pi

ADP and Pi
remain bound.

3:54 video https://www.youtube.com/watch?v=Ki6WjplSUcE

additional animation (not shown) http://

40

Table 9.2

Rigor Mortis
Rigor mortis the gradual stiffening of skeletal
muscles that begins several hours after death
and disappears about 48 hours after death.
Caused by the lack of ATP after death, thus the
breakage of the link between actin and myosin
does not occur.
Applications:
In forensic science to determine the approximate
time of death.
In meat industry, to prevent cold shortening,
electrical stimulation is carried out, immediately
after slaughter and skinning.

http://en.wikipedia.org/wiki/Rigor_mortis

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Relaxation

Figure 12.10c

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Online Tutorials
Neuromuscular Junction
https://
www.youtube.com/watch?v=7wM5_aUn2qs
Excitation-Contraction Coupling
https://www.youtube.com/watch?v=HJj3jUVDFFo
The Cross Bridge Cycle
https://www.youtube.com/watch?v=Ki6WjplSUcE

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