25/03/2021

Key concepts

SKELETAL MUSCLE • Muscle structure

• Sliding filament
and function
theory of muscle contraction

PHYSIOLOGY • Excitation-contraction coupling

• Recruitment, summation and tetanus
Topic 4
SLE211 Principles of Physiology
Trimester 1, 2021
Dr. Chris Lim
Reading: Chapter 8, pp 258-263

Key learning objectives

• Be able to describe the structure and function of the different types of muscle and
Muscle physiology
know where they are found in the body.
• Be able to describe the structure of the basic contractile unit of a skeletal muscle. • Contraction specialists in the body
• Understand the roles of tropomyosin, troponin and calcium ions in the regulation of
contraction in skeletal muscle. • Three types:
• Describe the structure and functions of the sarcoplasmic reticulum and transverse • Skeletal muscle: Attachment to the skeleton
tubular system in muscle contraction and relaxation.
• Be able to describe the events of the cross-bridge cycle and the role of ATP in this • Smooth muscle: Walls of hollow organs, tubes
cycle.
• Cardiac muscle: Walls of the heart
• Explain the process excitation-contraction coupling and the role of calcium ions in
this process.
• Describe the different mechanisms that allow a skeletal muscle to vary the amount Skeletal muscle Smooth muscle Cardiac muscle
of force it produces.
• Explain the events of a single twitch and events that occur during the latent period
• Understand how summation and tetanus can occur in a skeletal muscle fibre even
though skeletal muscle action potentials are all-or-nothing events.
• Explain three functions of ATP in skeletal muscle contraction and relaxation.
• Explain why creatine phosphate is important in generating ATP in early contractile
activity.
• Understand the different characteristics of muscle fibres that allow them to be
classified as fast-oxidative, slow-oxidative and fast-glycolytic.

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Muscle functions Muscle functions

• Muscle cells all have the ability to use chemical energy • Purposeful movement
to produce force and movement
• Manipulation of external objects

• Muscles are the largest group of tissues in the body – • Propulsion of contents through
approximately half of your body weight hollow internal organs
• 40% in men, 32% in women
• 10% smooth and cardiac muscle
• Expulsion of contents of organs
into the internal environment
(parturition)
• Muscles can develop tension or shorten to produce
movement
• Maintenance of homeostasis

Muscle similarities Categorisation of muscle

• All 3 types of muscle:
• Use the sliding filament mechanism of contraction
• Have thick and thin filaments
• Have contractile machinery that directly use ATP
• Require Ca2+ for cross bridge activity
• The 3 types of muscle are categorised according to
structure and control
• Fall into 2 categories based on appearance:
• Striated – due to light and dark bands that can be seen
under a microscope (skeletal, cardiac muscle)
• Unstriated (smooth muscle)

• Fall into 2 categories based on control:

• Voluntary control (innervated by SNS)
• Involuntary control (innervated by ANS)

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Categorisation of muscle Skeletal muscle functions

Striated Unstriated
muscle muscle • Attaches to skeleton via tendons
• Contraction supports and moves skeleton
Skeletal muscle Cardiac muscle Smooth muscle
• Acquiring food, chewing and swallowing
• Breathing – diaphragm and intercostals
• Allows the body to move away from harmful
situations
• Temperature regulation (generation)

Voluntary Involuntary
muscle muscle

Voluntary control = somatic innervation Involuntary control = autonomic innervation

Gross organisation of skeletal muscle Skeletal muscle cell structure

A) Whole muscle (an organ)
• Cells are large, elongated,
cylindrical shape – also called
fibres
• Fibres extend full length of muscle
B) Fascicle
Bundles of muscle fibres • Many muscle fibres lie parallel
to one another, bundled
C) Muscle fibre (cell) together by connective tissue

Bundles of myofibrils • Highly organised internal

structure - striated or striped
D) Myofibril - (intracellular structures) appearance
• Cells are multinucleated (fusion of
Bundles of myofilaments myoblasts)
• Contain many mitochondria (high
energy demand)
E) Myofilaments (cytoskeletal elements , thick (myosin) and thin (actin) filaments) Muscle fibre (i.e. cell)

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Skeletal muscle intracellular structure Skeletal muscle fibres are striated by a

• Muscle fibres are composed of
myofibrils
• specialised contractile elements
• 80% volume of muscle fibre
• Myofibrils are composed of individual
contractile proteins or myofilaments
(thick and thin filaments)
• Each myofibril consists of regular
arrangement of thick and thin
filaments:
• Thick filaments – myosin
• Thin filaments – actin (+ regulatory
proteins)
• Filaments form repeated set
arrangements within myofibril
segments (Sarcomeres)
highly organised internal environment
• Alternating dark bands (A bands) and
light bands (I bands) along myofibril
• A bands: made up of stacked set of
thick filaments along with portions of
thin filaments that overlap at both
ends
• I bands: consists of remaining portion
of thin filaments only that do not
project into A band
A band

I band

Muscle intracellular structure: Sarcomere

Functional unit of skeletal muscle Sarcomere
• Smallest component of a muscle fibre
that can contract • Each relaxed
sarcomere is ~2 µm
in width
• Z line
• defines boundary of sarcomere M line
• site where thin filaments attach • During growth, Z line Z line
muscle length Sarcomere
• H zone increases by adding
• lighter area within middle of A band new sarcomeres to
where thin filaments do not reach the end of the
• M line myofibril
• extends vertically down middle of A band
within centre of H zone
• system of supporting proteins that holds
thick filaments together vertically within
each stack I band A band
H zone

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Skeletal muscle intracellular structure:

Sarcomere support: Titin Myofilaments
• Largest protein in the body (~30,000 amino acids) • Myofilament is the term for the chains
• Functions: of (primarily) actin and myosin that pack
a myofibrils muscle fibre
• Structural support for thick filaments- sarcomere stability
• These are the force generating intracellular
• Acts as elastic spring and contributes to parallel elastic component of structures within muscles
muscle (along with elastic connective tissue)
• A single muscle fibre contains:
• Signals muscle strain via complex pathways to stimulate muscle
enlargement in response to resistance exercise – weight lifting • ~16 billion thick myosin filaments
• ~ 32 billion thin actin filaments
• Both filaments are intricately designed
and specifically arranged to permit
contraction of muscle

Thick filaments are composed of

Thick filaments are composed of myosin
myosin • Myosin heads (cross bridges) are the basic force-producing units of a
muscle
• Each thick filament contains around 300 myosin molecules • Myosin molecules are packed in a specific arrangement:
• Tails line up in the middle of the filament forming the backbone
• Myosin is a protein that is made up of 2 identical subunits -
each shaped like a golf club • Heads protrude outward at regular intervals

• Heads form cross bridges Cross bridges

(“linkages”) between thick and thin Myosin
molecules
filaments
Actin-binding site
• Each head (cross bridge) has two
Myosin ATPase site

important sites: Heads

• actin binding site
(b) Thick filament
• myosin ATPase (ATP-splitting) site
Tail • Half the myosin molecules are oriented in one direction and half in the
other - Important in force production
100 nm

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Myosin forms cross bridges Thin filaments

• Thin filaments consist of 3 proteins:
• Extend in 6 directions from each thick filament towards
• Actin
the surrounding thin filaments in the areas where the • Tropomyosin
thick and thin filaments overlap
• Troponin
• Formed by myosin heads
• Arrangement vital for functional interaction between
myosin and actin to permit contraction.
Cross Thin Thick
bridge filament filament

M line Z line A band I band

Portion of
myofibril

H zone
Thick Thin
filament filament Sarcomere A band I band

Tropomyosin (blocker)
Actin
• Actin is the primary structural protein in thin filaments • Thread-like protein that lies in the groove of the actin
• Each actin molecule is globular (spherical) in shape
spiral
• Actin filament resembles two strands of pearls twisted around each • When in the groove tropomyosin covers the myosin
other (double helical chain) binding site on the actin filament
• Each actin filament has a binding site for the myosin head • Blocks the interaction between actin and myosin (cross
bridge formation) that leads to muscle contraction –
tropomyosin is in this position in a relaxed muscle fibre
Binding site for
attachment with myosin
Actin molecules cross bridge

Tropomyosin Troponin
Actin helix

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Adrenergic receptors Actin + Tropomyosin + Troponin

= Thin filament
• Protein complex made of 3 polypeptide subunits
1. Troponin T - binds to tropomyosin
2. Troponin I – an inhibitory unit that binds to actin
3. Troponin C - binds to Ca2+
• Both troponin and tropomyosin help control the
interaction between actin and myosin involved in Thin filament
contraction – “regulatory proteins”

Tropomyosin is blocking myosin binding sites on actin

- Relaxed state
Tropomyosin Troponin

Summary
Actin + Tropomyosin + Troponin • Muscle- organised as bundles within bundles
= Thin filament • Much of the machinery for contraction is due to specialised intracellular
organisation

Thin filament

• When troponin is not bound to Ca2+ – it stabilises

tropomyosin in its blocking position over actin’s binding
sites for myosin – no contraction
• When Ca2+ binds to troponin, the shape of the protein
complex changes: Thin filament
• Tropomyosin moves away from blocking position
• Myosin binding sites on actin are exposed
Thick filament
• Actin and myosin can now bind and interact at cross bridges
• Contraction can occur

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Summary