Chapter 11

Skeletal Muscle

Additional reading: Vander’s Human Physiology – Chapter 9

What physiological properties do muscles have? What are the advantages compared to
servo motors? It is the material with its viscoelastic properties for one. This is an
important aspect, but there are many more muscle properties which make a big
difference compared to actuation used in engineering, as we will explore in this
Chapter 11.
For additional reading> Vander’s chapter 9.

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What we will cover today:

1. Introduction to different muscle types in the body and their functions

2. Lever systems
3. Muscle anatomy and function of skeletal muscle
4. Skeletal muscle histology
5. Skeletal muscle contraction
6. Energy requirements and supply
7. Neuro-muscular junction

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 1. Different muscle types in the body
Skeletal muscle: is attached to bones, found in your
legs, arms and torso throughout the entire muscular-
skeletal system.Voluntary. Multinucluated. Striated.
Function: => holding the skeleton together, acting
against gravity to keep us upright, enable movements;
help to maintain normal body temperature.

Cardiac muscle: is found in the heart wall.

Involuntary. Uni-binucleated. Striated.
Function: => pumping blood.

Smooth muscle: found in the wall of hollow internal

organs; e.g. intestine, stomach, bladder, blood vessels.
Involuntary. Uni nucleated.
Function: => move substances (digestion and waste
removal), keeping shut functional compartments,
controlling blood flow.

Figure 11.1

Figure 11.1: Different muscle types in the body. Explanation on the slide.

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 The Body
1.2 The musculoskeletal system: Bone and skeletal muscles are interdependent
Body systems
SKELETAL SYSTEM
The skeleton can be divided into two subgroups, the axial
skeleton and the appendicular skeleton. The axial skeleton
consists of the bones of the skull (cranium), vertebral
column, ribs, and sternum, whereas the appendicular
skeleton consists of the bones of the upper and lower limbs
(Fig. 1.12).
The skeletal system consists of cartilage and bone.

Skeletal system:
Cartilage
it needs muscles
Cartilage is an avascular form of connective tissue consist-

to support our default posture

ing of extracellular fibers embedded in a matrix that con-
tains cells localized in small cavities. The amount and kind
of extracellular fibers in the matrix varies depending on the
and to generate movements
type of cartilage. In heavy weightbearing areas or areas
prone to pulling forces, the amount of collagen is greatly
increased and the cartilage is almost inextensible. In con-
trast, in areas where weightbearing demands and stress are
less, cartilage containing elastic fibers and fewer collagen
fibers is common. The functions of cartilage are to:

■ support soft tissues,

■ provide a smooth, gliding surface for bone articulations
at joints, and
■ enable the development and growth of long bones.

There are three types of cartilage:

■ hyaline—most common; matrix contains a moderate

amount of collagen fibers (e.g., articular surfaces of
bones);
■ elastic—matrix contains collagen fibers along with a
large number of elastic fibers (e.g., external ear);
Axial skeleton
■ fibrocartilage—matrix contains a limited number of
cells and ground substance amidst a substantial amount Appendicular
skeleton
of collagen fibers (e.g., intervertebral discs).

Cartilage is nourished by diffusion and has no blood

vessels, lymphatics, or nerves. Figure 11.2
Fig. 1.12 The axial skeleton and the appendicular skeleton.

Figure 11.2: Bones and muscles constitute the muscular-skeletal system. No current humanoid
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robot can match the capabilities of the entire muscular-skeletal system in combination with its finely
tuned movements coordinated by the nervous system … as yet – and probably not in many years to
come. (Though, specific motor tasks have been massively advanced due to machine learning).
You won’t have to learn ALL the different muscles by heart … .
https://www.nlm.nih.gov/exhibition/historicalanatomies/bougle_home.html

4
 Tendon Tendon

Triceps Biceps

Tendon
Tendon

2. How do muscles move limbs? Final PDF t

2.1 Agonist/antagonist relationship (because muscle can only pull)

Triceps
Biceps
relaxes
relaxes
Biceps
Tendon Tendon contracts

Triceps Biceps

Tendon Quadriceps
Tendon Triceps
femoris
contracts

Extension Flexion

Gastrocnemius
Tendon = muscle to bone

Figure 11.3
Figure 9.27 Antagonistic muscles for flexion and
Biceps extension of the forearm.
contracts
Figure 11.3: Agonist/antagonist relationship. You have seen similar figures in the
Neuro lectures where we looked into reflex control.
action From those lectures you know
of the gastrocnemius—extension of the that
foot at the ankle
normally the state of the joints (during reflexes)joint to stand on tiptoe.
is controlled by muscles
The muscles, bones, and
based on
joints in the body
theare arranged in
calf can
Quadriceps Quadriceps relaxed,
activity ofTriceps
propriorecetors, where the contraction ofsystems—a
lever antagonistic muscle
good example ofisthe
femoris avoided.
generalfemoris
principle of physi-
contracts
Only if precise movements are performed voluntarily,
ology thata physiological
moderate co-contraction
processes of
relaxed are dictated by the laws of
contracts
chemistry and physics. The basic principle of a lever is illustrated 1 cm,
antagonists may occur. by the flexion of the arm by the biceps muscle (Figure 9.29),
Extension Flexion muscle
which exerts an upward pulling tension on the forearm about 5 cm moves
In the elbow joint, the biceps brachii and the triceps brachii
away from build
the elbow a pair
joint. In thisof antagonistic
example, a 10 kg weight held in
Gastrocnemius greater
flexor and extensor muscles, respectively. Theythe control the joint angle applying
hand exerts a downward load of 10contracts the 35 cm from the
kg about amplif
mechanisms of a lever system. elbow. A law of physics tells us that the forearm is in mechani- tively s
cal equilibrium when the product of the downward load (10 kg) of the h
N/B: ‘Bi-’ and ‘Tri-’ mean 2 and 3, obviously, referring to the
and its distance fromnumber
the elbowof
(35muscle
cm) is equal to the product of even th
the isometric
elements in the biceps and triceps brachii supporting flexiontension
andexerted by the muscle (X) and its distance
extension. this ve
from the elbow (5 cm); that is, 10 × 35 = X × 5. Thus, X = 70 kg.
Figure 9.27 Antagonistic muscles for flexion and The important point is that this system is working at a mechanical
extension of the forearm. disadvantage because the tension exerted by the muscle (70 kg) is
9.7 S
considerably greater than the load
Flexion of leg (10 kg) it is supporting.
Extension of foot A num
However, the mechanical disadvantage that most muscle tion of
action of the gastrocnemius—extension of the foot at the ankle lever systems operateFigure under
9.28 is offset byofincreased
Contraction maneuver-
the gastrocnemius muscle ininthe
the
joint to stand on tiptoe. ability. Ascan
calf illustrated
lead eitherintoFigure of the when
flexion 9.30, leg, if the biceps shortens
the quadriceps the is
femoris muscle mu
The muscles, bones, and joints in the body are arranged in 282 relaxed, or9to extension of the foot, if the quadriceps is contracting.
Chapter
lever systems—a good example of the general principle of physi-
ology that physiological processes are dictated by the laws of
chemistry and physics. The basic principle of a lever is illustrated 1 cm, the hand moves through a distance of 7 cm. Because the
by the flexion of the arm by the biceps muscle (Figure 9.29), muscle shortens 1 cm in the same amount of time that the hand
which exerts an upward pulling tension on the forearm about 5 cm moves 7 cm, the velocity at which the hand moves is seven times
wid03885_ch09_257-300.indd 282

away from the elbow joint. In this example, a 10 kg weight held in greater than the rate of muscle shortening. The lever system
the hand exerts a downward load of 10 kg about 35 cm from the amplifies the velocity of muscle shortening so that short, rela-
elbow. A law of physics tells us that the forearm is in mechani- tively slow movements of the muscle produce faster movements
cal equilibrium when the product of the downward load (10 kg) of the hand. Thus, a pitcher can throw a baseball at 90 to 100 mph
and its distance from the elbow (35 cm) is equal to the product of even though his arm muscles shorten at only a small fraction of
the isometric tension exerted by the muscle (X) and its distance this velocity.
from the elbow (5 cm); that is, 10 × 35 = X × 5. Thus, X = 70 kg.
The important point is that this system is working at a mechanical
disadvantage because the tension exerted by the muscle (70 kg) is
9.7 Skeletal Muscle Disorders 5
 Direction attached to a fi
Movement of force
of load
Gastrocnemius Tendon Exte
muscle retinacu
Fulcrum
2. How do muscles move limbs? Overlies ten
2.2 Limbs are moved by lever systems (third class lever). running to the
of the h
Movement
Biceps brachii of load Ten
muscle

Tendon
Transv
ligam
Cross-br
Direction the ten
of force Fulcrum

THIRD-CLASS LEVER
Tendon sh
The most common type of lever in the body; the Protects d
force is applied between Figurethe
11.4 load and the fulcrum. ten
An example is flexing the elbow joint (the fulcrum)
Figure 11.4: Lever
bysystem in limb joints
contracting the isbiceps
a third-class lever.muscle.
brachii Third-class lever is the most common
type of lever used in the human body. In this type of lever, the force is applied between the
72

resistance (weight) and the axis (fulcrum). It is similar to a situation where someone is using a shovel
to pick up an object. First and second-class levers are also observed in the human body.

Credit: The concise human body book (https://www.dk.com/uk/book/9780241395523-the-concise-

human-body-book/)

US_072-073_MusclesandTendons.indd 72

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3. Muscle anatomy from the macroscopic to
the microscopic scale

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3.1 Traverse section of the left thigh
Nerve Skin

Subcutaneous fat layer:

pathway for blood vessels and
nerves before they divide and
enter the muscles

Fascia: a layer of tough

connective tissue holding
together those elements which
serve the same function
Bone
(fascicle)
Blood vessels and nerves

Figure 11.5

Figure 11.5: Internal elements of a muscle. This slide shows the different anatomical
elements of a muscle that is moving the thigh. Just underneath the skin there is a sub-
cutaneous layer that contains the fat. Normally, the amount of subcutaneous fat is
significantly higher in women than in men. It serves as an energy reserve which –
originally – was meant to enable females to make it through an energetically expensive
pregnancy. A decrease of the overall body fat component below 8 and 14% of the total
body mass in men and women, respectively, may result in health problems. In women
the menstrual cycle may be interrupted (=> they become temporary infertile).

Fascia consist of connective tissue which encloses muscle tissue, or fascicles,

controlling the same degree of freedom in terms of movements. In between fascicles
blood vessels and nerves run which provide oxygen/nutrients and control muscle
contraction, respectively.

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 and undergo mitotic proliferation. Daughter cells then differenti- The term muscle refers to a number of skeleta
ate into myoblasts that can either fuse together to form new fibers fibers bound together by connective tissue (Figure 9.2
or fuse with stressed or damaged muscle fibers to reinforce and muscles are usually attached to bones by bundles of c
repair them. The capacity for forming new skeletal muscle fibers is tissue consisting of collagen fibers known as tendons.

Tendons
3.2 Muscle
anatomy
Connective
tissue
Muscle

Muscle fiber (single muscle cell)

Blood
vessel

Muscle => fascicle => muscle fibre (muscle cell) => myofibril A band I band
Myofibril
Connective tissue: is continuous with the tendons
Nerves: dense (not shown)
Z line Z line
Blood supply: large and very variable
Muscle fibres: consist of a bundle of myofibrils and build a
syncytium Sarcomere

M line
Figure 11.6
Z line Z line

Figure 11.6: From muscles to microfibrils – anatomical organization of the biceps

brachii. A fascicle consists of multiple muscle fibres (muscle cells). They build a
syncytium, which is basically the fusion of several cells. This means that muscles cells
H zone
are ‘multi-nucleated’ (have multiple nuclei).

Figure 9.2
Structure of a skeletal muscle,
a single muscle fiber, and its
component myofibrils. Thick (myosin) filament Thin (actin) filament
Muscle

wid03885_ch09_257-300.indd 259 11/

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 3.3 Morphology of a muscle fibre: from
myofibrils to sarcomere Sarcolemma (plasma membrane) Final PDF to printer

Sarcoplasm
Sarcoplasmic reticulum
Sarcoplasmic reticulum
Myofibrils
Transverse T tubules
Cytosol
Mitochondria
Plasma
membrane (Myoglobin)
Muscle fibres contain
Transverse
tubules Myofibrils, which are organised
Opening of
transverse tubule
to extracellular fluid
in repeated units called
Terminal cisternae Sarcomeres, these are the
Mitochondrion
active elements.
Figure 9.6 Transverse tubules and sarcoplasmic reticulum in a single skeletal muscle fiber.
Myofibrils are made of Sarcomeres
9.2 Molecular Mechanisms of muscle fiber. A single motor neuron innervates many muscle fibers,
but each muscle fiber is controlled by a branch from only one motor
Skeletal Muscle Contraction Figure 11.7
neuron. Together, a motor neuron and the muscle fibers it inner-
The term contraction, as used in muscle physiology, does not vates are called a motor unit (Figure 9.7a). The muscle fibers in a
necessarily mean “shortening.” It simply refers to activation of the single motor unit are located in one muscle, but they are distributed
force-generating sites within muscle fibers—the cross-bridges. throughout the muscle and are not necessarily adjacent to each other
For example, holding a dumbbell steady with your elbow bent (Figure 9.7b). When an action potential occurs in a motor neuron,
requires muscle contraction but not muscle shortening. Following all the muscle fibers in its motor unit are stimulated to contract.

Figure 11.7: Morphology of a muscle fibre. This slide shows a detailed illustration of a
contraction, the mechanisms that generate force are turned off and
tension declines, allowing relaxation of muscle fibers. We begin
The myelin sheath surrounding the axon of each motor neu-
ron ends near the surface of a muscle fiber, and the axon divides
into a number of short processes that lie embedded in grooves on
muscle fibre (muscle cell). The membrane, sarcolemma, separates the cell from the
our explanation of how skeletal muscles contract by first describ-
ing the mechanism by which they are activated by neurons. (You the muscle fiber surface (Figure 9.8a). The axon terminals of a
may find it helpful to review the electrical basis of neuronal func- motor neuron contain vesicles similar to those found at synaptic
extracellular space. Muscle fibres contain sarcoplasm, equivalent to the intracellular
tion by referring back to Chapter 6.) junctions between two neurons. The vesicles contain the neuro-
transmitter acetylcholine (ACh). The region of the muscle fiber

Junction fluid (cytoplasm) and an organelle called sarcoplasmic reticulum that stores and
Membrane Excitation: The Neuromuscular plasma membrane that lies directly under the terminal portion of
the axon is known as the motor end plate. The junction of an axon
controls the release of Ca . Characteristic features of muscle fibres are transvers T
Stimulation of the neurons to a skeletal muscle is the only mech-
anism by which action potentials are initiated in this type of mus-
2+ terminal with the motor end plate is known as a neuromuscular
junction (Figure 9.8b).

tubules which form an extension of the sarcolemma and invade the muscle cell and
cle. In subsequent sections, you will see additional mechanisms
for activating cardiac and smooth muscle contraction.
Figure 9.9 shows the events occurring at the neuromuscular
junction. When an action potential in a motor neuron arrives at
The neurons whose axons innervate skeletal muscle fibers the axon terminal, it depolarizes the plasma membrane, opening
are known as alpha motor neurons (or simplyclose
thus establish a proximity between the functional subunits, microfibrils, and the
as motor neurons), voltage-sensitive Ca2+ channels and allowing calcium ions to dif-
and their cell bodies are located in the brainstem and the spinal fuse into the axon terminal from the extracellular fluid. This Ca2+
extracellular
cord. The axons space.
of motor neurons are myelinated Microfibrils
(see Figure
and are the largest-diameter axons in the body. They are therefore
6.2) consist of series of sarcomeres which contain the
binds to proteins that enable the membranes of ACh-containing
vesicles to fuse with the neuronal plasma membrane (see Figure
molecular
able to propagate machinery
action potentials at for
high velocities, allowing
nals from the central nervous system to travel to skeletal muscle
sig- muscle contraction (thick and thin filaments; Z discs). Muscle
6.27), thereby releasing ACh into the extracellular cleft separating
the axon terminal and the motor end plate.
fibres also contain a high concentration of myoblobin (related to haemoglobin), an
fibers with minimal delay (review Figure 6.24).
Upon reaching a muscle, the axon of a motor neuron divides
ACh diffuses from the axon terminal to the motor end plate
where it binds to ionotropic receptors of the nicotinic type (see

oxygen binding molecule, and a large number of mitochondria which produce ATP –
into many branches, each branch forming a single synapse with a
262 Chapter 9
Chapter 6, Section 6.10). The binding of ACh opens an ion channel

the energy source for muscle contraction.

wid03885_ch09_257-300.indd 262 11/27/17 02:55 PM

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4. Muscle histology-microscopic views
Light microscopic view
• Multinucleated, fused cells – (syncytium).
• Striation across the muscle fibres -
suggesting regularity of structure.
• Myosin and Actin filaments are
responsible for the striation

Electron micrograph

Figure 11.8

Figure 11.8: Microscopic appearance of muscles. The name ‘striated muscle’ come
from the repetitive structures within the sarcomeres, specifically the Z discs/lines and
the M lines shown on the previous slides. The light microscopy image shows the
‘striation’ (left). Electron microscopy reveals a detailed image of the various lines and
zones. It is the ordered arrangement of specific proteins, Myosin and Actin filaments,
that causes the regular pattern typical of striated muscle.

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5.1 Subcellular analysis: Structure of Myosin and Actin

Actin
Thin filament

Myosin
Thick filament

Figure 11.9

Figure 11.9: Molecules producing movements. Myosin (thick filaments) has a

characteristic shape with ‘heads’ attached, which, in pairs of opposing
orientation form so-called ‘crossbridges’. Myosin interacts with Actin (thin
filaments) through the so called ’cross bridges’

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5.2 Model of a Sarcomere

Repeated components in a
Sarcomere:
• Myosin
• Actin
• Titin

and, associated with Actin:

• Nebulin
• (Tropomyosin
• Troponin)

Note the regular arrangement – also that of the Z and M lines and the H, A and I bands.
Which components define these structures?
Figure 11.10

Figure 11.10: This schematic model of the sarcomere shows all proteins involved in the
process of muscle contraction. It illustrates very well which parts of the filaments cause
the different bands and lines in the microscopic images. It also includes a key molecule,
titin, which basically acts like a spring and contributes to the muscles’ passive elastic
properties. Nebulin, yet another protein, is potentially involved in the regulation of thin
filaments’ length during the assembly of sarcomeres (function not entirely clear).

A band: anisotropic band

I band: isotropic band

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5.3 Sliding Filament Theory of muscular contraction

relaxed

partially contracted

maximally contracted

The width of the H zone and the I band is reduced, but the A band width stays unchanged. Actin filaments (yellow) slide into
the spaces between the Myosin filaments (red) and are pulling the Z discs toward each other.
Figure 11.11

Figure 11.11: The sliding filament theory explains microscopic images of different contraction states
(relaxed, partially contracted, fully contracted). If the myosin filaments themselves did change their
length, the width of the A band should be reduced. Instead, the H zone and the I band are reduced,
suggesting that actin filaments slide into the space between the myosin filaments. The next slide explains
how this is done.

On the right: you could compare the connectivity of the different molecules making a sarcomere with a
person standing between two bookcases. In this case the book case are the z bands. The person act as the
myosin and pulls them in via ropes (actin). The pulling arms would be analogous to the cross bridges. (z
bands are also called z discs.)

14
5.4 What is the role of calcium in muscle contraction?

For the contraction Tropomyosin and troponin

to occur you need

2 elements:
1) Ca2+ Actin
2) ATP Myosin

Actin binding site

ATP binding site

Figure 11.12

Figure 11.12: Molecules producing movements. Myosin (thick filaments) has a characteristic shape
with ‘heads’ attached, which, in pairs of opposing orientation form so-called ‘crossbridges’. Myosin
interacts with Actin (thin filaments) which is accompanied by Troponin and Tropomyosin. Actin
has myosin head binding sites but the Tropomyosin covers (in the resting muscle fibre) these binding
sites to which myosin heads attach during a contraction. Calcium presence allows to move
tropomyosin fibers and uncover the myosin binding sites on the actin filament. The troponin which
is bound to tropomyosin is the calcium binding protein allowing the tropomyosin conformation
change to occur and free the actin binding sites for the crossbridges.

15
5.4 What is the role of calcium in muscle contraction?

Tropomyosin and troponin

Actin

Ca2+
5.4 What is the role of calcium in muscle contraction?

Tropomyosin and troponin

Actin
Myosin binding site
Myosin binding site
Figure 11.13
Ca2+

Myosin

Figure 11.13

Figure 11.13: The role of calcium in producing sarcomere contraction. Calcium presence allows to
move tropomyosin fibers and uncover the myosin binding sites on the actin filament. The troponin
which is bound to tropomyosin is the calcium binding protein allowing the tropomyosin
conformation change to occur and free the actin binding sites for the crossbridges.

16
5.4 What is the role of calcium in muscle contraction?

Calcium binds to Troponin. This moves the Troponin/Tropomoysin complex to expose the
Myosin binding sites on the Actin fibres, allowing Actin and Myosin to interact.
Without Calcium, Myosin cannot bind to Actin.
Calcium is stored in the Sarcoplasmic reticulum. Depolarisation of the sarcolemma and the
T-tubules opens Ca2+ channels in the sarcoplasmic reticulum. After activation, Ca2+ is
pumped back into the sarcoplasmic reticulum.
How and when this is happening we will see at the end of this lecture…

What about ATP? What is its role?

17
5.5 Mechanics of the Sliding filament Theory of muscular
contraction

• Myosin head groups interact with Actin binding sites and ‘slide’ the filaments past one
another WITHOUT shortening their length.
• The contraction of the muscle fibres is generated by the movement of the Myosin head
groups.
• This active event, the ‘power stroke’, requires energy in form of ATP and a significant
concentration of Ca2+ in the sarcoplasm.

Figure 11.14

Figure 11.14: Mechanism of sliding filament theory. Neither the myosin nor the actin
filaments change their length. The myosin head groups form a hinge with the central
myosin filament. Movement of the hinges pulls the myosin filament into the open space
between the actin filaments. This movement is called the ‘power stroke’ and depends
on ATP and a sufficient Ca2+ concentration in the sarcoplasm.

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5. 5 The Power Stroke
Cross bridge
binds to actin
1. bound ATP is hydrolysed => AF
ADP ADP
Myosin is energised and 2 Pi 3
Pi
relaxed (+Ca2+)
2. in the presence of Ca2+ => MF
Weakly bound
cross-bridge binds to actin
3. => power stroke occurs while Powerstroke (1) -Pi
ADP and Pi are released ATP hydrolysis (2) -ADP
Cross bridge
4. => first Myosin is still attached moves
to Actin, but when Myosin
binds another ATP molecule it ATP +ATP
detaches from Actin 1 4
This cycle repeats itself as long as Cross bridge
ATP and Ca2+ are present. detaches Strongly bound

What about ATP? Where does the energy for muscle contractions come from?
Figure 11.15

Figure 11.15: Events during the power stroke. Explanation on slide.

19
 contraction in terms of the sliding-filament mechanism. Stretch- (Figure 9.22): (1) phosphorylation of ADP by creatine phosphate
ing a relaxed muscle fiber pulls the thin filaments past the thick (a small molecule produced from three amino acids and capable
filaments, changing the amount of overlap between them. Stretch- of functioning as a phosphate donor), (2) oxidative phosphoryla-
ing a fiber to 175% of L0 pulls the filaments apart to the point tion of ADP in the mitochondria, and (3) phosphorylation of ADP
where there is no overlap. At this point, there can be no cross- by the glycolytic pathway in the cytosol.
bridge binding to actin and no development of tension. As the fiber
shortens toward L0, more and more filament overlap occurs and
the tension developed upon stimulation increases in proportion Creatine Phosphate
to the increased number of cross-bridges in the overlap region. Phosphorylation of ADP by creatine phosphate (CP) provides a very
6. Energy for muscle activity
Filament overlap is ideal at L0, allowing the maximal number
of cross-bridges to bind to the thin filaments, thereby producing
rapid means of forming ATP at the onset of contractile activity. When
the chemical bond between creatine (C) and phosphate is broken, the
6.1 Energy sources maximal tension.
The tension decline at lengths less than L0 is the result of
amount of energy released is about the same as that released when
the terminal phosphate bond in ATP is broken. This energy, along
several factors. For example, (1) the overlapping sets of thin fila- with the phosphate group, can be transferred to ADP to form ATP in
Skeletal muscles are mostlyments
in resting states
from opposite ends and
of the rarely
sarcomereinmayintense bursts
interfere with the of aactivity. Whencatalyzed
reversible reaction active,by the enzyme creatine kinase:
their energy source is ATP:cross-bridges’ ability to bind and exert force; and (2) at very short
lengths, the Z lines collide with the ends of the relatively rigid thick
creatine
kinase

filaments, creating an internal resistance to sarcomere shortening. CP + ADP ! C + ATP

ATP => ADP + phosphate + energy
Muscle fiber
Blood

Different ATP sources:

Creatine phosphate ADP + Pi
1. Creatine phosphate (1 1
Myosin-ATPase contraction
Ca2+-ATPase relaxation
ATP) Creatine ATP

2. Aerobic cellular Glycogen

3 2
Amino acids Proteins
respiration Oxidative
Glucose Glycolysis phosphorylation
3. Anaerobic cellular Fatty acids
Lactic acid
respiration
Oxygen

3. 2. & 3. use Glucose to Fatty acids

produce 2 ATP
Figure 9.22 The three sources of ATP production during muscle contraction: (1) creatine phosphate, (2) oxidative phosphorylation, and
(3) glycolysis.
Which source of ATP is used depends on the duration and strength of the muscle contraction. Figure 11.16
Muscle 275

Figure 11.16: Energy for muscle activity.

wid03885_ch09_257-300.indd 275 11/27/17 02:55 PM

Initial and very intense activity uses anaerobic sources of energy:

At rest the fibres produce ATP and Creatine phosphate (1). Creatine phosphate provides the energy for
muscle contraction initially by transferring the phosphate residual to ADP molecules. As a result the ATP
concentration is kept at a reasonably high level, while the Creatine phosphate concentration is rapidly
decreasing. Once Creatine phosphate reserves are depleted oxidative phosphorylation in mitochondria
kicks in for the next 5-10 minutes based on breakdown of glycogen and glucose.
Glycolysis produces 2 ATP from Glucose (from blood and Glycogen stores). This generates Pyruvate and
Lactate. Lactate is recycled in the liver. Build up of Lactate is one factor leading to fatigue (3)
Long term exercise requires the use of aerobic respiration in the Mitochondria using loads of O2 (from
blood and myoglobin, Mb).
Though enabling long-term exercise, it supports mostly low intensity exercise because the enzymes
involved are slow and the process depends on the rate of oxygen delivery.
Other substrates, e.g. fatty acids, may also be used for ATP production by similar oxidative processes
which lead to O2 debt post exercise. Therefore blood supply needs to increase so that
more oxygen is delivered to and fuel is produced (ATP) in the muscle.

20
6.2 Regulation of blood supply

• Large amounts of O2 and Glucose have to be delivered. CO2, Lactate and other waste needs
to be removed during and after exercise.
• A large blood supply all the time would be wasteful. Therefore muscles have many blood
vessels, but the arterioles are constricted at rest to reduce the blood supply.
• The muscular vasculature has highly developed metabolic autoregulatory activity → arteriolar
dilatation in the presence of low O2, high CO2, low pH etc.

21
How does the muscle know when to contract?

The ‘neuromuscular junction’

22
7.The neuromuscular junction
Muscle contraction requires the activity of an alpha motor neuron (cf. ch 6). The synapse
between the motor neuron and the muscle is called the neuromuscular junction, NMJ.
Each muscle fibre is innervated by only one motor neuron, but most motor neurons will
control more than just one muscle fibre.

All muscle fibres contacted by the same

motor neuron are called a motor unit.

Figure 10.17

23
7.1 Structure of the NMJ
Motor nerve fiber
Axon terminal Myelin
Axon terminal
Synaptic bulb
Synaptic vesicles containing Synaptic vesicles
neurotransmitter (Acetylcholine, ACh) containing ACh
Synaptic cleft
Motor endplate has invaginations, junctional
folds Why?
ACh receptors on the muscle membrane Sarcolemma Synaptic
cleft

Region of sarcolemma Junctional fold

with Ach receptors

Figure 10.18

Figure 10.18: Structure of the neuromuscular junction. ACh is used as an excitatory

neurotransmitter. The invaginations at the postsynaptic specializations increase the surface area at
which the transmitter can act.

24
 7.2 Sequence of events at the NMJ

1. Action potential arrives 1

2. Depolarization opens Ca2+ channels,
Ca2+ flows into terminal
3. ACh is released from the pre-synaptic
2
terminal into the synaptic cleft
4. ACh diffuses through the cleft and Ca2+
binds to its post-synaptic receptor 6
5. Channels for Na+ and K+ opened 7
6. Depolarization causes action potentials
3
in the muscle
7. ACh is degraded to choline and acetate 4
by acetylcholinesterase (AChE); choline 5
is taken back into the presynaptic
terminal WHY?

Figure 10.19

Figure 10.19: What happens at the neuromuscular junction? The processes are similar to those at chemical
synapses in the central nervous system, CNS. Some marked differences are (i) a different excitatory
neurotransmitter (CNS = glutamate versus ACh at the NMJ), and (ii) muscle fibres do not have receptors for
inhibitory synapses.
After ACh is broken down into choline and acetyl, the former is transported back to the presynaptic terminal
for recycling. If AChE did not beak down ACh, the muscle would be constantly activated.

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7.3 Excitation-contraction
Coupling
1
1. Depolarisation of the sarcolemma
2. The T tubules opens Ca2+ channels in
the sarcoplasmic reticulum (SR). This
2
rapidly increases the concentration
Ca2+ Ca2+
of Ca2+ in the sarcoplasm.
3. The Troponin/Tropomoysin complex
Ca2+ 4
moves to expose the Myosin binding
sites on the Actin fibres allowing Actin 3
and Myosin to interact.
4. This, in turn, induces muscle
contraction as long as there is ATP
available.
5. Ca2+ is actively pumped back into SR.
Figure 10.20

Figure 10.20: Excitation and contraction. Explanation on slide.

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Summary chapter 11

• Muscles and bones together constitute the muscular-skeletal system.

• Skeletal muscles have a characteristic ‘striated’ appearance when inspected under the microscope,
which is the result of a regular pattern produced by repetitive arrangements of myosin and actin
filaments.
• The ‘siding filament theory’ describes the processes which result in muscle contraction. Key events
include the ‘power stroke’ where myosin head groups interact with actin filaments in the presence of
Ca2+ and ATP causing the muscle fibres to shorten.
• Muscles are activated by motor neurons which release ACh at the neuromuscular junction that
generates a muscle action potential that causes Ca2+ influx into the sarcoplasm followed by muscle
contraction.

Next lecture: smooth and cardiac muscles

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