Dr. Kennon M.

Garrett

MUSCLE CONTRACTION

Reading: Widmaier et al., Vander’s Human Physiology, 15th ed., Chapter 9.

Learning Objectives

1. List and describe the structure and proteins that make up skeletal muscle fibers, including
sarcomeres.
2. Describe the sliding filament mechanism of muscle contraction.
2. List the steps of the cross bridge cycle.
3. Describe the functions of myosin, actin, troponin and tropomyosin.
4. List the steps of excitation-contraction coupling.
5. Describe how intracellular Ca++ levels increase and are regulated during muscle contraction.
6. List the steps involved in producing a muscle contraction beginning with the excitation of a
neuron in the cerebral cortex through sequestration of Ca++ and relaxation of the muscle.

I. Organization of muscle

A. Types of muscle

84
 1. Striated – banding pattern in muscle seen under polarized light. Banding is due to
organization of myofilaments within the muscle cell.

a. Skeletal muscle – connected to bone & responsible for movement of skeleton,

under voluntary control

b. Cardiac muscle - heart muscle, spontaneous contractions regulated by the

autonomic nervous system.

2. Smooth – bundles of muscle fibers surrounding hollow organs or tubes, regulated

by the autonomic nervous system, local chemical signals and hormones.

B. Skeletal muscle structure

The whole skeletal muscle is made up of bundles of muscle cells. The bundles are called
fascicles, and are surrounded by connective tissue

Muscle fibers –Muscle cells are called muscle fibers. Within the fascicle are muscle
fibers. Skeletal muscle fibers are oriented along the longitudinal axis of the muscle.

Muscle fiber cell division stops at birth, however, fibers can increase in size. If muscle
cells are injured, satellite cells can differentiate into muscle cells after birth.

85
C. Fine structure of muscle

1. Myofibrils
cylindrical bundles of thick and thin filaments within the muscle fiber surrounded
by sarcoplasmic reticulum.

86
2. Sarcomere

The myofibril consists of a regular linear repeat of structures called sarcomeres which
are the functional unit of a muscle fiber. A sarcomere is made up of thick and thin
filaments and extends from a Z-line to the next Z-line.

3. Striations – banding pattern of skeletal muscle fibers seen under polarized light.

a. A bands – dark bands produced by overlapping myosin and actin

b. I bands – light bands where there is only actin, area between thick
filaments in 2 adjacent sarcomeres bisected by the Z-line.

87
4. Thick filaments - myosin.

heavy chain (2)

light chain (4)

One myosin molecule is comprised of 2 heavy chains and 4 light chains.

cross bridge - globular region of myosin that projects toward thin filament

Myosin filaments are oriented with their tails point toward the center of the
sarcomere.

88
5. Thin filaments - composed of three types of proteins

Actin - globular proteins that polymerize together to form two intertwined

helical chains. Each actin molecule contains a binding site for myosin.

Tropomyosin - a regulatory protein that wraps around the actin chain and at rest
covers the myosin binding site on actin.

Troponin - a regulatory protein that holds tropomyosin over the myosin

binding sites on actin.

Cross-bridge
binding sites
Actin

Troponin
Tropomyosin

c. Z-line – a network of proteins that bind to the thin filaments. A sarcomere

is defined by filaments between two adjacent Z lines.

d. titin – connects myosin to Z-line

89
II. Molecular mechanism of contraction

A. Sliding filament mechanism

1. Shortening of sarcomeres

I-band shortens, but A-band length does not change, thick and thin filaments slide
past each other, but thick and thin filaments do not shorten.

2. Swinging of cross bridges, thin filaments and Z-lines are pulled toward the center
of the sarcomere.

90
B. Four steps of the cross bridge cycle

1. “Energized” Cross bridge binds to actin.

2. Pi is released from myosin head and cross bridge rotates (power stroke) and pulls
actin filaments toward center of sarcomere. ADP is then released from the cross
bridge.

3. ATP binds to myosin head and causes cross bridge to detach ("plasticizing" action
of ATP).

4. ATP is hydrolyzed to Pi and ADP and “energizes” cross bridge.

5. The next cycle begins

C. Role of ATP in cross bridge cycle

1. Hydrolysis of ATP "energizes" the cycle.

2. Binding of ATP to myosin breaks the cross bridge linkage to actin. If no ATP
is available, the cross bridge remains attached to the actin producing rigor mortis.
Rigor mortis peaks approximately 12 hrs after death and disappears 48-60 hrs
after death due to break down of muscle.
91
 D. Regulator proteins

1. Tropomyosin – intertwines with actin and covers myosin binding sites on actin

2. Troponin binds to tropomyosin and holds tropomyosin over myosin binding site.
a. tropinin has 3 subunits: inhibitory (I), Calcium-binding (C) and
tropomyosin-binding (T)

b. Ca2+ binding sites are on troponin (C subunit).

c. Binding of Ca2+ to the C subunit of troponin causes conformational change

of troponin and causes tropomyosin to move aside and exposes the myosin
binding sites on actin.

III. Excitation - contraction coupling

A. Microanatomy

1. Sarcoplasmic reticulum (SR) – endoplasmic reticulum-like organelles that

store Ca2+ in skeletal (and cardiac) muscle fibers. The SR surrounds the
myofibrils.

Lateral sacs (terminal cisternae) are enlargements at the end of sarcoplasmic

reticulum and are associated with the transverse tubule.
92
2. Transverse tubules (T-tubules) – invaginations of the muscle plasma membrane
(sarcolemma).

3. Voltage-gated Ca2+ channels (L-type Ca2+ channels, also called

dihydropyridine receptors or DHP receptors) are located in the T-tubules

4. Ca2+ release channels (also called ryanodine receptors) in lateral sacs of the
sarcoplasmic reticulum. Activation of these channels allows Ca2+ to flow out of
the sarcoplasmic reticulum into the cytoplasm.

Voltage-gated Ca2+ channels in T-tubules are physically linked to Ca2+ release

channels in sarcoplasmic reticulum.

5. Ca2+-ATPase in sarcoplasmic reticulum membrane pumps cytosolic Ca2+ into the

sarcoplasmic reticulum.

93
B. Events of excitation-contraction coupling

1. Action potentials traveling down sarcolemma from the end plate enter the T-
tubules and activate voltage-gated Ca2+ channels.

2. Activation of the voltage-gated Ca2+channels activates Ca2+ release channels

causing release of Ca2+ from the lateral sacs of the sarcoplasmic reticulum.

3. Ca2+ binds to troponin removing the blocking action of tropomyosin.

4. Myosin cross-bridges bind to actin and cycle at least 100 times.

5. Ca2+-ATPase pump Ca2+ from the cytosol into the sarcoplasmic reticulum

6. Sequestration of Ca2+ into the SR decreases the cytosolic Ca2+ concentrations

7. Ca2+ dissociates from troponin and cross-bridge cycling ceases.

8. The sarcomere extends to its resting length

94
C. Duration of twitch – approximately 100 msec

95
IV. REVIEW

Natural history of neuromuscular action

A. Synaptic activity

1. Integration of synaptic input - excitatory vs. inhibitory

2. Summation - temporal and spatial

3. Depolarization of initial segment of axon to threshold

4. Generation of action potential

5. Conduction of action potential down axon

6. Depolarization of nerve terminal

7. Excitation - Secretion coupling by influx of Ca2+

8. Release of neurotransmitter

9. Activation of postsynaptic receptor

10. Summation of EPSPs and IPSPs, then repeat the process

B. Sequence of events in activating skeletal muscles

1. Activation of motor neuron cell body leads to an action potential in the motor
neuron.

2. Action potential at nerve terminal of motor neuron causes release of acetylcholine

at neuromuscular junction.

3. Acetylcholine activates nicotinic receptors in the endplate, producing an end-plate

potential.

4. The end-plate potential depolarizes the surrounding muscle membrane and

produces an action potential.

5. The action potential propagates to the end of the muscle fiber.

96
C. Sequence of events at skeletal muscle fiber

1. Action potentials enter transverse tubules and activate voltage-gated Ca2+

channels (DHP receptors).

2. Ca2+ is released from sarcoplasmic reticulum via Ca release channels

3. Ca2+ binds to troponin.

4. Tropomyosin moves to uncover myosin binding sites on actin

5. Cross bridge cycling begins

6. Ca2+-ATPase pumps Ca2+ back into SR

7. Ca2+ dissociates from troponin

8. Tropomyosin covers myosin binding sites and cross bridge cycling ends

97