Anatomy & Physiology I

Skeletal muscle

Javier Torres Fernández

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 Index
1. Introduction to the muscular system physiology
2. Muscle types
3. Skeletal muscle
4. Control of skeletal muscle activity
5. Contraction and relaxation of muscle fiber
6. Stimulation frequency
7. Muscular fatigue

© Copyright Universidad Europea. Todos los derechos reservados 2

1. Muscular tissue
Responsible for the movement of organisms and their organs

Contraction: ability of cells to shorten their length

The contractile capacity depends on the association between actin

microfilaments and the myosin II motor proteins present in the cytoskeleton.

Muscle cells are usually arranged in parallel forming bundles or sheets (muscle
bundles)

Vascularized and innervated

 1. Muscular system
Through sustained contraction or isolated contraction and relaxation, muscle tissue performs 5 important
functions:

PRODUCTION OF BODY MOVEMENTS

STABILIZING BODY POSITIONS

ORGAN VOLUME REGULATION

DISPLACEMENT OF SUBSTANCES WITHIN THE ORGANISM

HEAT GENERATION
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2. Muscle types

Skeletal muscle

Cardiac muscle

Smooth muscle
2. Muscle types

2. Muscle types
General characteristics of the muscle tissues:
SKELETAL MUSCLE
•Acts on the skeleton (joints).
• Voluntary control (SNC).
• Maintenance of posture,
speech, breathing, etc.
• Striated muscle.
CARDIAC MUSCLE
•It acts on the heart.
• Involuntary control (ANS).
• It is also a striated muscle.
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SMOOTH MUSCLE
• It lines hollow viscera such
as the intestine and vessels.
• It does not have the
striations of the skeletal and
cardiac muscles.
• Involuntary control (ANS).
3. Skeletal muscle
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3. Skeletal muscle
Skeletal muscle is made up of thousands of multinucleated elongated cylindrical cells
called muscle fibers, which are parallel to each other.

Each muscle fiber contains numerous cylindrical structures called

myofibrils, which are arranged along its longitudinal axis.
3. Skeletal muscle

 Terminology used in Muscle Physiology:

GENERAL TERM EQUIVALENT IN MUSCLE

MUSCLE CELL MUSCLE FIBER

CELLULAR MEMBRANE SARCOLEMA

CYTOPLASM SARCOPLASM

ENDOPLASMIC RETICULUM SARCOPLASMIC RETICULUM

 3. Skeletal muscle
MUSCLE FIBER
A myofibril can be divided longitudinally into sarcomeres, which are delimited by
two dark lines called Z lines and represent a contractile length in skeletal muscle.
MYOFIBRILS

SARCOMERS

BANDS

FILAMENTS
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3. Skeletal muscle I BAND

THIN FILAMENTS: ACTIN

A BAND

THICK FILAMENTS:
MYOSIN
THIN FILAMENTS:
ACTIN

H ZONE OVERLAP ZONE

MYOSIN MYOSIN
(only) & ACTIN
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3. Skeletal muscle
• On each side of the Z disc is a clear band (I band), which contains fine filaments, made
up of a protein called actin.

• The area located between two I bands of a sarcomere are A bands, which contains thick filaments
corresponding mainly to the myosin protein, which overlap at the ends of the band with thin actin
filaments.

• The fine actin filaments extend

from the Z discs to the center of the
sarcomere, overlapping part of the
thick filaments. The dark area at the
end of A bands represents the
region of overlap between fine and
thick filaments.
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3. Skeletal muscle
• The clear area located in the center of the sarcomere is called the H zone. It corresponds to the
region of the A band that contains thick myosin filaments, but not thin actin filaments.

• The M line includes proteins essential for the organization and alignment of the thick filaments
of the sarcomere.
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3. Skeletal muscle
https://www.youtube.com/watch?v=f_tZne9ON7c&t=40s

Electron microscopy of a skeletal muscle fiber showing the ultrastructure of the myofibril
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3. Skeletal muscle
In addition, each myofibril is surrounded by a sarcoplasmic reticulum (SR), which is an intracellular
network of membranes that participates in the regulation of intracellular calcium.

The transverse tubules (T tubules) tunnel from the surface to the center of each muscle fiber.
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Boron y Boulpaep: Medical Physiology, 2ºed

3. Skeletal muscle
We can find several type of proteins in each myofibril of muscle fibers:

MYOFIBRILAR PROTEINS

CONTRACTILE REGULATORY GIANT ACCESSORY

PROTEINS PROTEINS PROTEINS

ACTIN TROPONIN TITINE

MYOSIN TROPOMYOSIN NEBULIN
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3. Skeletal muscle
 Contractile proteins

Thin actin filaments

The fine filament is formed by the aggregation of actin molecules

(globular actin or G actin).

Each actin molecule contains a myosin binding site.

The actin aggregates clump together in a helical arrangement

to form two strands of filamentous actin or F actin.

The thin filaments are attached to the Z line.

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3. Skeletal muscle
 Regulatory proteins

In addition, there are two regulatory proteins in the fine filaments that allow muscle fibers to start or
stop contracting:

TROPOMYOSIN TROPONIN

Tropomyosin is a fibrillar protein, which in a

Troponin is a protein that consists of 3 subunits:
resting state covers the active sites of G-actin,
preventing their interaction with the myosin
- I: affine for actin
- T: affine for tropomyosin
heads. - C: affine for calcium
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3. Skeletal muscle
 Regulatory proteins

The binding of calcium with troponin C stimulates the movement of tropomyosin over the actin filament,
exposing the myosin binding sites and facilitating the interaction of the actin and myosin filaments and
thereby the contraction of the sarcomere.
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3. Skeletal muscle
 Contractile proteins

Thick myosin filaments

• Each thick filament is made up of hundreds

of myosin molecules.

• Each myosin molecule consists of two

interlocking subunits.

• Each of the subunits has a long tail and a fat,

protruding head.
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3. Skeletal muscle
 Contractile proteins

Thick myosin filaments

• The head is the main end of myosin,

because it is the part that generates the
mechanical force of a muscle.

• For this, it has an actin-binding site and an

ATPase site that hydrolyzes ATP.
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3. Skeletal muscle
 Contractile proteins

Thick myosin filaments

• The heads are called transverse bonds

(cross-bridges), because they sometimes bridge
the thick and thin filaments.

• The myosin molecules are attached to each

other at the end of the tails, so that their heads
extend in opposite directions, away from the
center.
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3. Skeletal muscle
 Accessory giant proteins

TITIN NEBULIN

Titin serves two functions:

• Stabilizes the position of the myosin Nebulin helps align the actin filaments in the
filaments. sarcomere.
• Its elasticity returns the stretched muscles to
their resting length.
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3. Skeletal muscle

 Sliding filament mechanism

• During muscle contraction, the myosin heads of the thick filaments act on the thin actin filaments and
determine their glide towards the center of the sarcomere.

• As the filaments glide, the I bands and H zones progressively narrow until, when the muscle is fully
contracted, they disappear. Band A is not shortened.

• The sliding of the filaments and the shortening of the sarcomeres determine the contraction of the muscle
fibers.
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3. Skeletal muscle
 Sliding filament mechanism
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4. Control of skeletal muscle activity

Skeletal muscle movement is voluntary, so it is controlled by the CNS.

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4. Control of skeletal muscle activity

In muscle, nerves branch, so that each branch innervates a single muscle fiber.

A neuron and all the muscle fibers it stimulates make up a

motor unit.
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4. Control of skeletal muscle activity

The ends of the axons of the motor neurons are larger, and form the synaptic terminal bulbs, which contain
synaptic vesicles that house the neurotransmitter involved in movement, which is acetylcholine (ACh).

The neuromuscular junction

formed by the axon terminal
and the muscle is called the
motor end plate.
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5. Contraction and relaxation of muscle fiber

Muscle fiber excitation

Excitation-contraction coupling

Contraction cycle
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5. Contraction and relaxation of muscle fiber

 How is the excitation of a neuron to a muscle fiber produced?

1. The arrival of the nerve impulse to the synaptic terminal bulb increases permeability to calcium,
which penetrates the terminals and facilitates the release of acetylcholine vesicles to the synaptic cleft.

2. ACh binds to its receptors (nicotinic) on the endplate, which favors the entry of sodium into the
cell, generating an action potential, which spreads through the sarcolemma and T-tubules through the
rest of the myofibrils.

NOTE: The effect of ACh is brief because it is rapidly degraded by acetylcholinesterase (AChE) in the synaptic cleft.
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5. Contraction and relaxation of muscle fiber

NERVE IMPULSE

 How is the excitation of a neuron to a muscle fiber produced?

ACh RELEASE

ACh - R
UNION

ACTION
POTENTIAL

MUSCLE FIBER
EXCITATION
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NERVE IMPULSE

ACh RELEASE

ACh - R
UNION

ACTION
POTENTIAL

MUSCLE FIBER
EXCITATION
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5. Contraction and relaxation of muscle fiber

 The contraction cycle

• The action potential in the muscle fiber causes the release of calcium stored in the sarcoplasmic
reticulum (SR).

• The released calcium binds with troponin molecules in the fine filaments: this determines a
modification in the form of troponin, which causes the troponin-tropomyosin complex to be released from
the myosin-binding sites present in actin.

• After the release of the myosin binding sites, the contraction cycle begins, which is a repetitive
sequence of a series of events that causes the filaments to slip.
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5. Contraction and relaxation of muscle fiber

 The contraction cycle

(1) ATP hydrolysis. As mentioned earlier, a myosin head includes an ATP-binding site that functions as
an ATPase, an enzyme that hydrolyzes ATP into ADP (adenosine diphosphate) and a phosphate group.
The energy generated from this hydrolysis reaction is stored in the myosin head for later use during the
contraction cycle. The myosin head is said to be energized when it contains stored energy. The energized
myosin head assumes a “cocked” position, like a stretched spring. In this position, the myosin head is
perpendicular (at a 90º angle) relative to the thick and thin filaments and has the proper orientation to
bind to an actin molecule. Notice that the products of ATP hydrolysis (ADP and a phosphate group) are
still attached to the myosin head.
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5. Contraction and relaxation of muscle fiber

 The contraction cycle

(2) Attachment of myosin to actin. The energized myosin

head attaches to the myosin-binding site on actin and
releases the previously hydrolyzed phosphate group. When
a myosin head attaches to actin during the contraction
cycle, the myosin head is referred to as a cross-bridge.
Although a single myosin molecule has a double head, only
one head binds to actin at a time.
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5. Contraction and relaxation of muscle fiber

 The contraction cycle

(3) Power stroke. After a cross-bridge forms, the myosin head

pivots, changing its position from a 90º angle to a 45º angle relative
to the thick and thin filaments. As the myosin head changes to its
new position, it pulls the thin filament past the thick filament toward
the center of the sarcomere, generating tension (force) in the
process. This event is known as the power stroke. The energy
required for the power stroke is derived from the energy stored in the
myosin head from the hydrolysis of ATP (see step 1 ). Once the power
stroke occurs, ADP is released from the myosin head.
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5. Contraction and relaxation of muscle fiber

 The contraction cycle

(4) Detachment of myosin from actin. At the end of the

power stroke, the cross-bridge remains firmly attached to
actin until it binds another molecule of ATP. As ATP binds to
the ATP-binding site on the myosin head, the myosin head
detaches from actin.

The contraction cycle repeats as the myosin ATPase

hydrolyzes the newly bound molecule of ATP, and continues
as long as ATP is available and the Ca2+ level near the thin
filament is sufficiently high.
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5. Contraction and relaxation of muscle fiber

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5. Contraction and relaxation of muscle fiber

 The contraction cycle

An increase in Ca2+ concentration in the sarcoplasm starts muscle

contraction, and a decrease stops it. When a muscle fiber is relaxed, the
concentration of Ca2+ in its sarcoplasm is very low, only about 0.1 micromole
per liter (0.1 μmol/L). However, a huge amount of Ca2+ is stored inside the
sarcoplasmic reticulum. As a muscle action potential propagates along the
sarcolemma and into the T tubules, it causes the release of Ca2+ from the SR
into the sarcoplasm and this triggers muscle contraction. The sequence of
events that links excitation (a muscle action potential) to contraction (sliding
of the filaments) is referred to as excitation–contraction coupling.
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5. Contraction and relaxation of muscle fiber

 Excitation-contraction coupling:

Excitation-contraction coupling occurs at the triads of the skeletal muscle fiber. Recall that a triad consists
of a transverse (T) tubule and two opposing terminal cisternae of the sarcoplasmic reticulum (SR). At a
given triad, the T tubule and terminal cisternae are mechanically linked together by two groups of integral
membrane proteins: voltage-gated Ca2+ channels and Ca2+ release channels.
Voltage-gated Ca2+ channels are located in the T tubule membrane; they arranged in clusters of four known
as tetrads. The main role of these voltage-gated Ca2+ channels in excitation-contraction coupling is to serve
as voltage sensors that trigger the opening of the Ca2+ release channels. Ca2+ release channels are
present in the terminal cisternal membrane of the SR. When a skeletal muscle fiber is at rest, the part of the
Ca2+ release channel that extends into the sarcoplasm is blocked by a given cluster of voltage-gated Ca2+
channels, preventing Ca2+ from leaving the SR.
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5. Contraction and relaxation of muscle fiber

 Excitation-contraction coupling:

When a skeletal muscle fiber is excited and an action potential travels along the T tubule, the voltage-gated
Ca2+ channels detect the change in voltage and undergo a conformational change that ultimately causes
the Ca2+ release channels to open. Once these channels open, large amounts of Ca2+ flow out of the SR into
the sarcoplasm around the thick and thin filaments. As a result, the Ca2+ concentration in the sarcoplasm
rises tenfold or more. The released calcium ions combine with troponin, which in turn undergoes a
conformational change that causes tropomyosin to move away from the myosin-binding sites on actin.
Once these binding sites are free, myosin heads bind to them to form cross-bridges, and the muscle fiber
contracts.
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5. Contraction and relaxation of muscle fiber

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5. Contraction and relaxation of muscle fiber

When a person dies, calcium begins to leak out of the SR and binds with
troponin, triggering the slipping of the thin filaments.

However, since the body no longer produces ATP, the cross-bridges cannot be
separated from actin.

The resulting stiffness is called cadaveric stiffness or rigor mortis, which is the
rigidity of death.
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5. Contraction and relaxation of muscle fiber

There are two conditions that will cause a muscle fiber to relax after contracting:

The breakdown of ACh by the enzyme

acetylcholinesterase, which determines the termination
of muscle action potentials

The closure of the channels that release calcium to the

sarcoplasm, so that the calcium is trapped in the SR
membrane
 Cessation
Tema 8 of nerve
stimulation
and ACh release

ACh splitting by
acetylcholinesterase
(AChE)

Reabsorption of calcium
ions in the SR

Loss of calcium
ions by troponin

Return of tropomyosin to
position active actin site
blocking
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5. Contraction and relaxation of muscle fiber

In summary:

IF THE MUSCLE FIBER RELAXES IF THE MUSCLE FIBER IS EXCITED

(NOT CONTRACTED). (CONTRACTS).

THE CALCIUM CONCENTRATION IN THE

THE CALCIUM CONCENTRATION IN THE
SARCOPLASM IS REDUCED.
SARCOPLASM INCREASES.
(THE CALCIUM IS TRAPPED INSIDE THE
(THE CALCIUM COMES OUT OF THE SR).
SR).

ATP IS CONSUMED IN BOTH PROCESSES

https://www.youtu
be.com/watch?v=
sZuy356qkPM

In summary:
• Period between the arrival of
the action potential and the
beginning of the contraction.
Latent
period
• It begins after the latency
period and ends when the
muscle contraction reaches
its peak.
• It coincides with the increase
in calcium levels in the
sarcoplasm.
Contraction
period
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• It is the longest phase and
comprises the time between
the maximum tension and
the end of the contraction.
• It coincides with the
decrease in calcium levels
and the number of
transverse bonds.
Relaxation
period
 ¿…?

MYASTENIA GRAVIS. Myasthenia gravis is caused by a defect in the transmission of nerve impulses to the
muscles. It occurs when normal communication between the nerve and the muscle is disrupted at the
neuromuscular junction, the place where nerve cells connect with the muscles they control. In
myasthenia gravis, antibodies block, alter, or destroy acetylcholine receptors at the neuromuscular
junction, preventing muscle contraction from occurring. These antibodies are produced
by the body's own immune system. Therefore, myasthenia gravis is an autoimmune
disease, because the immune system, which normally protects the body from external
organisms, attacks itself by mistake. In addition, the postsynaptic folds have been
shown to be flattened or "simplified", decreasing the efficiency of transmission.
Commons.wikimedia.org
Acetylcholine is released normally, but the potentials generated are of less intensity
than necessary.
 ¿…?

Tubocurarine (also known as d-tubocurarine or DTC) is a toxic benzylisoquiniline alkaloid found in the
Chondodendron tomentosum plant known for its use as arrow poison. It competes with ACh for binding
to Rs and action potentials are not initiated. May cause death when muscles involved in pulmonary
ventilation are affected.

Commons.wikimedia.org
 Tema 8

6. Stimulation frequency
• A single action potential generates a weak muscle contraction.

• If a second stimulus appears before the complete relaxation of the muscle fiber, the second contraction is more
intense than the first because it begins when the fiber has a higher tension level. This phenomenon, by which
successive stimuli produce more intense contractions, is called wave summation.

• When a fiber is stimulated faster (20-30 stimuli / second), it can only partially relax between stimuli. The result is
an incomplete or unfused tetanus contraction. When stimulated at more than 80-100 stimuli / second, it does not
relax. The result is a complete or fused tetanus contraction.
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6. Stimulation frequency
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7. Muscular fatigue
The inability of a muscle to contract strongly after prolonged activity is called muscle fatigue, due
to a decrease in:

• Release of calcium from SR

• Glycogen

• Creatine phosphate

• Oxygen
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7. Muscular fatigue
It is due to the accumulation of waste products and lack of nutrients.

Intramiofibrillar Glycogen is the main regulator of Muscle Function, as a source of glycogenolytic

energy that it represents.

Glycogen-RS complex is not only related to glycogenolysis, but also to glycolysis. In this line, the
relationship with the availability of Glucose has also been related to this regulatory process of
muscle contraction.

Therefore, the role of Nutrition before and during exercise, ensuring adequate initial Glycogen
levels and maintaining adequate glucose availability that guarantees a constant glycolytic flow is
decisive, since this glycolytic flow will, in turn, regulate the own glycogenolysis.
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7. Muscular fatigue
Phosphocreatine is part of a pair of reactions relating muscular fatigue.
The energy released in a reaction is used to regenerate another compound, ATP. Phosphocreatine
plays a particularly important role in tissues that have a high and fluctuating demand for energy,
such as the brain or muscle, acting as an energy transport element from the mitochondria to the
area of the cells where ATP is needed and as a temporary
storage of energy (buffer) for intense and short uses.

Also neuromuscular fatigue can affect the effectivity of

muscular contraction, by the lack in release of ACh by neurons.
 In summary…
https://www.youtube.com/watch?v=NfEJUPnqxk0&t=627s
https://www.youtube.com/watch?v=Vs0tZV35_pw

• Skeletal muscle is made up of multinucleated muscle fibers covered by a

sarcolemma with extensions called transverse tubules. Each fiber contains
myofibrils that are organized into functional units called sarcomeres.

• Sarcomeres are made up of thin actin filaments and thick myosin filaments.

• Muscle contraction occurs when the myosin heads attach to the actin
filaments at both ends of the sarcomere and walk along them, causing the
fine filaments to move towards the center of the sarcomere, with
consequent shortening of the sarcomere.

© Copyright Universidad Europea. Todos los derechos reservados 64

 In summary…
• The arrival of a nerve impulse to the motor endplate causes high amounts of
calcium to be released from the SR, which allows the start of the contraction
cycle.

• The summation of waves is the increase in the force of a contraction that

occurs when a second stimulus arrives before the complete relaxation of
the muscle contracted by the previous stimulus.

• Repetitive stimuli can produce an unfused tetanus contraction, which is a

sustained muscle contraction with partial relaxation. Stimuli that are
repeated more frequently cause a fused tetanic contraction, which is a
sustained contraction with no partial relaxation between stimuli.

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 Thanks for
your attention!
JAVIER.TORRES@
universidadeuropea.es

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© Copyright Universidad Europea. Todos los derechos reservados