SKELETAL MUSCLE
Dr. Hoe See Ziau
Department of Physiology
Faculty of Medicine
University of Malaya
Muscle Tissues
Muscles in human body
Specialised excitable tissues
~ 50 % body weight
Ability to contract
Contractions provide movements
Do work
Move body or limbs
Push, pull or hold an external load or object
Mix or move food through the gastrointestinal track
Pump blood out of the heart to the blood vessels
Contract uterus for birth of foetus
Micturition and defaecation
Types of Muscle
Three types of muscle:
1. Skeletal muscle
2. Cardiac muscle
3. Smooth muscle
Types of Muscle
Skeletal Muscle Cardiac Muscle Smooth Muscle
striated striated non-striated
voluntary involuntary involuntary
Basic Characteristics of Muscle Tissues
Excitability
Response to stimuli
Conductivity
Able to conduct action potential
Contractibility
Able to shorten in length
Extensibility
Stretches when pulled
Elasticity
tends to return to original shape & length after contraction
or extension
Skeletal Muscle
Attached to bones & moves skeleton
Makes up 40% of BW in men and
32% of BW in women
Main functions of skeletal muscle:
Initiate movements
Perform work
Maintain posture
Stabilise joints
Generate heat
Level of Organisation in Skeletal Muscle
Skeletal Muscle
(organ)
(fascicle)
Fascicle
(bundle of muscle fibres)
Muscle Fibre
(cell)
Myofibril
Sarcomere
Filaments
(Thin – actin)
(Thick - myosin)
Membranes of Skeletal Muscle
Muscle surrounded by epimysium
Bundles of fibres (fascicles) surrounded by perimysium
Muscle fibre surrounded by endomysium
These connective tissues extend beyond the ends of
muscle to form tendons that attach muscle to bones
Skeletal Muscle Fibre
Large, elongated, shape like Transverse tubules (T-tubules)
cylinder – internal conduction system
10 – 100 µm in diameter, up Myofibrils for contraction
to 750,000 µm (0.75 m) in
Sarcomeres – regular
length (extend entire length
arrangement of thin (actin) &
of muscle)
thick (myosin) filaments
Multinucleated with
Actin filaments interdigitate
abundant of mitochondria
with myosin filaments
Sarcolemma (cell membrane)
Appears striated under
Sarcoplasm (muscle cell microscope
cytoplasm)
Sarcoplasmic reticulum
(modified ER)
Structure of a Skeletal Muscle Fibre
Electron Micrograph of Skeletal Muscle
Sarcomere
• The functional unit of skeletal muscle
• Multi-protein complexes composed
different filament systems:
Thin filament system
Thick filament system
Sarcomere
sarcomere
Sarcomere
Sarcomere
Sarcomere
Sarcomere
A band (dark band)
consists of a stacked set of thick filaments
I band (light band)
Consists of the array of thin filaments, and is the region where
they do not overlap the thick filaments
H zone
The lighter area in the centre of A band where the thin filaments
do not overlap with thick filaments
M line
Consists of supporting proteins that hold the thick filaments
together vertically within each stack
Z line
Consists of supporting proteins that hold the thin filaments
together vertically within each stack
Area between two Z lines is called a sarcomere
Thin Filament
Actin
Spherical in shape, with a special binding site for attachment with myosin
cross bridge
Joined into two strands and twisted together to form the backbone of a
thin filament
Tropomyosin
Threadlike proteins that lie end-to-end alongside the groove of the actin
spiral
Covers active sites of actin
Troponin complex
binds to actin & holds tropomyosin in place
Thin Filament
Thin Filament
Troponin Complex
TnT – binds to tropomyosin
TnC – binds to Ca2+
TnI – binds to actin
Thick Filament
Each thick filament is composed
of several hundred myosin
molecules packed together
A single myosin protein looks like
2 golf clubs with shafts twisted
about one another
Myosin molecules have
elongated tails & globular heads
Heads form cross-bridges
between thick and thin filaments
during contraction
Thick Filament
Cross Bridges
Each cross bridge has two
important sites:
An actin-binding site
A myosin ATPase site
Organisation of Actin and Myosin
Thin filaments are arranged
hexagonally around thick
filaments
Cross bridges Each thin filament is surrounded
by 3 thick filaments
Cross bridges project from each
thick filament in all 6 directions
toward the surrounding thin
filaments
Contraction of Muscle Fibres
Done by sliding actin filaments
Contraction of Muscle Fibres
Contraction of Muscle Fibres
Sliding Filament Theory
Contraction occurs by actin filaments sliding into
myosin filaments
Actin filaments move, myosin filaments remain
stationary
Sarcomeres shortened
Cause whole muscle to contract
Contraction of Muscle Fibres
Role of Calcium
Ca2+ released from
sarcoplasmic reticulum
Ca2+ binds to troponin C
Troponin turns, moves
tropomyosin & exposes actin
active site
Contraction of Muscle Fibres
Role of Calcium
Myosin head binds to actin
active site, form cross-bridge,
move & produces powerful
strokes
Actin slides in – muscle fibre
contracts
Cross-bridge action continues
while Ca2+ is present
When action potential stops,
Ca2+ is pumped back to SR
Tropomyosin covers back
actin’s active site
Relaxation occurs
Contraction of Muscle Fibres
Role of Calcium
Contraction of Muscle Fibres
Role of ATP
ATP split by myosin ATPase ; ADP and Pi
remain attached to myosin; energy is stored
within the cross bridge
Mg2+ must be attached to ATP before ATPase
2
can split the ATP
Ca2+ released on excitation, removes
inhibitory influence from actin → energised
1 3 myosin cross bridge bind with actin
Cross bridge bends and causes power stroke
ADP and Pi are released after power stroke is
completed
4
ATPase site is free for attachment of another
ATP
Attachment of new ATP permits detachment
of cross bridge
Contraction of Muscle Fibres
Contraction of Muscle Fibres
All the cross bridges’ power strokes are directed
toward the centre of the sarcomere
All 6 of the surrounding thin filaments on each end
of the sarcomere are pulled inward simultaneously
Contraction of Muscle Fibres
Rigor Mortis
“Stiffness of death” – a generalised
locking in place of skeletal muscle that
begins 3 to 4 hours after death
Following death, [Ca2+]i begins to rise
This Ca2+ moves the regulatory proteins
aside, permitting actin bind with the
myosin cross bridges, which were
already charged with ATP before death
No fresh ATP available after death, actin
and myosin remain bound in rigor
complex
Resulting in stiffness condition of dead
muscles
Electrical Properties of Muscle Fibres
Resting membrane potential: -90mV
When an adequate stimulus is given
Membrane potential (mV)
→ action potential
Maximum potential: +30mV
Depolarisation is due to influx of Na+
-90
Time taken: 1 – 2 msec
Absolute refractory period & relative
refractory period present
Action potential results in muscle
contraction
Action Potential and Muscle Twitch
Latent period
The delay between stimulation
and the onset of contraction (a
Tension
few msec)
Contraction time
The time from the onset of
contraction until peak tension is
developed (average ~ 50 msec)
Membrane potential (mV)
Relaxation time
The time from peak tension until
relaxation (~ 50 msec or more)
A single contraction/relaxation
-90
cycle is called a muscle twitch
Excitation-Contraction Coupling
Refers to the series of events linking muscle
excitation (electrical events) to muscle contraction
(mechanical events)
Electrical events – presence of action potential
Mechanical events – cross-bridge activity
Electrical events come first before mechanical
events
Ca2+ is the link between excitation and contraction
Excitation-Contraction Coupling
Transverse Tubules (T tubules)
The surface membrane at
each junction of A band and
I band dips into muscle fiber
to form a T tubule
Action potential on the
surface membrane spreads
down into the T tubule
The presence of local action
potential in T tubule induces
permeability changes in the
sarcoplasmic reticulum
Excitation-Contraction Coupling
Sarcoplasmic Reticulum (SR)
Modified endoplasmic
reticulum
Consists of a fine network of
interconnected compartments
surrounding each myofibril
Separate segments of SR are
wrapped around each A band
and each I band
The ends of each segment
expand to form lateral sacs,
which store Ca2+
Excitation-Contraction Coupling
Release of Ca2+ from SR
When action potential is
propagated down the T tubules,
local depolarisation activates the
voltage-gated dihydropyridine
receptors in T tubule
These activated receptors in turn
trigger the opening of Ca2+-
release channels (alias
ryanodine receptors) in adjacent
lateral sacs of SR
Ca2+ is released into the
surrounding sarcoplasm
Relaxation of Muscle Fibres
When ACh is removed from the neuromuscular junction, the muscle
fibre action potential ceases
No longer a local potential in T tubules to trigger Ca2+ release
Released Ca2+ is pumped back into the lateral sacs by Ca2+-ATPase
pump
Removal of sarcoplasmic Ca2+ allows the troponin-tropomyosin
complex to slip back into its blocking position
Actin and myosin are no longer able to bind at the cross bridges
Thin filaments are able to return passively to their resting position
Relaxation occurs
Excitation-Contraction Coupling
Excitation-Contraction Coupling and Relaxation
Summary of Events
1. Ach released from the terminal of a motor 6. Actin slides in, muscle fibre contracts
neuron initiates an action potential in the resulting in contraction of whole
muscle fibres muscle
2. Muscle action potential travels down T 7. ADP and Pi are released after the
tubule power stroke is complete
3. Causes SR to release Ca2+ into 8. New ATP binds to myosin head;
sarcoplasm detachment of the cross bridge
4. Ca2+ binds to troponin, exposing actin’s 9. Cross-bridge action continues while
cross-bridge binding sites Ca2+ is present
5. Myosin head binds to active site, form 10. When action potential stops, Ca2+
cross-bride, moves and produces power pumped back to SR
stroke
11. Tropomyosin covers back active sites
12. Relaxation occurs
Contraction of Whole Muscles
Even when muscle are at rest, certain amount of
tautness usually remain → muscle tone
Results from a low rate of nerve impulses coming
from the spinal cord
To maintain a normal posture
Contraction of Whole Muscles
Whole muscles are groups of muscle fibres bundled
together
Muscle fibres in each muscle can function
cooperatively to produce contractions of variable
grades of strength
When the whole muscles contract, tension is created
Gradation of whole muscle tension depends on
The number of muscle fibres contracting within a
muscle
The tension developed by each contracting fibre
Motor Unit
Each whole muscle is innervated by a
number of different motor neurons
One motor neuron innervates a number
of muscle fibers
Each muscle fiber is supplied by only
one motor neuron
A motor neuron plus all the muscle
fibres it innervates is called a motor unit
When a motor neuron is activated, all
the muscle fibres in that motor unit are
stimulated to contract simultaneously
Each muscle consists of a number of
intermingled motor units
Motor Unit
Precise control of movement determined by
number and size of motor units
The number of muscle fibres innervated by
one motor neuron – innervation ratio
The bigger the ratio of nerve to muscle fibres, the
coarser the movement will be
Examples:
1:4 – fine movements (external eye muscle)
1:200-300 – Coarse movements (back muscle)
1:150 – on average
Motor Unit
Motor Unit Recruitment
For a weak contraction of the whole muscle,
only a few of its motor units are activated
For stronger and stronger contractions, more
and more motor units are stimulated to
contract → motor unit recruitment
Motor Unit Recruitment
At minimum stimulus strength
only motor units with low threshold will contract
At maximum stimulus strength
all motor units contract
↑ strength of stimulus
↑ recruitment of motor units
↑ contraction
Mechanical Properties of Skeletal Muscle
Muscle Twitch
A twitch is a single contraction/ relaxation cycle
Mechanical Properties of Skeletal Muscle
Muscle Twitch
If the muscle has completely relax before the next stimulus
takes place
A second twitch of the same magnitude as the first occurs
• When a muscle begins to
contract, its initial strength
of contraction may be as
Maximum tension (in treppe)
little as ½ of its strength 10
to 50 muscle twitches later
• The strength of contraction
increase to plateau
(Treppe)
Mechanical Properties of Skeletal Muscle
Summation and Tetanus
Summation
If the muscle is restimulated before it has completely relaxed, the
2nd twitch is added on to the 1st twitch, resulting in summation
Tetanus
When the muscle is stimulated so rapidly that it does not have an
opportunity to relax between stimuli, a maximal sustained
contraction occurs → tetanus
Mechanical Properties of Skeletal Muscle
Summation and Tetanus
When muscle is stimulated, Ca2+ is released from SR → cross-
bridges → contraction
When stimulation ceases, Ca2+ is pumped back into SR
If the 2nd stimulation occur far enough apart in time for all the
released Ca2+ from the 1st contractile response to be pumped
back into SR
→ an identical twitch response occurs
With rapid stimulation, there is not enough time between
successive stimulations to remove all the Ca2+ from the
sarcoplasm
→ Ca2+ levels in the sarcoplasm increase → more active cross-
bridges → a stronger contraction → summation occurs
Mechanical Properties of Skeletal Muscle
Response of muscle to repeated stimulation
As strength of stimulation increases gradually, more
& more motor unit will be activated
→ recruitment
As frequency of stimulation increases gradually,
contraction will increase more & more, then become
sustained
→ summation & tetanus
Mechanical Properties of Skeletal Muscle
Muscle Fatigue
When the stimulation is given repeatedly at a fast rate
Contraction becomes weaker & weaker gradually
Contraction becomes more irregular
Until no contraction occur
Fatigue occurs
Mechanical Properties of Skeletal Muscle
Fatigue Type
Muscle fatigue
Occurs when an exercising muscle can no longer respond to stimulation with the
same degree of contractile activity
Causes:
Accumulation of lactic acid
Depletion of energy stores
supply of O2 and nutrients
Central fatigue
Occurs when the CNS no longer adequately activates the motor neurons
supplying the working muscles
Neuromuscular fatigue
Depletion of acetylcholine
Mechanical Properties of Skeletal Muscle
Length-tension relationship
At each determined muscle length:
Without stimulation → passive tension
With stimulation → total tension
Active tension = total tension – passive tension
Mechanical Properties of Skeletal Muscle
Length-tension relationship
In general, tetanic tension develop initial
muscle length (within limit)
For every muscle → an optimal length at which
maximal force can be developed
In the body, relaxed length of muscle are also the
optimal length
Capable of obtaining maximal tetanic
contractions & maximal force
Mechanical Properties of Skeletal Muscle
Length-tension relationship
Mechanical Properties of Skeletal Muscle
Types of Contraction
1. Isotonic contraction
Tension developed – constant
Muscle length – changes
For
Body movement
Moving an external load or object
2. Isometric contraction
Muscle length – constant
Tension developed – changes
For
Holding a load or object
Mechanical Properties of Skeletal Muscle
Isotonic Contraction
The muscle length changes to move a load
Mechanical Properties of Skeletal Muscle
Isometric Contraction
Tension in the muscle increases but the
muscle fibres neither shortened or
lengthened
Mechanical Properties of Skeletal Muscle
Isotonic Isometric
Skeletal Muscle Metabolism
Contraction-relaxation process requires ATP in
three different steps:
1. Splitting of ATP by myosin ATPase provides energy for the
power stroke of the cross bridge
2. Binding of fresh ATP molecule to myosin permits
detachment of the bridge from actin filament at the end of
power stroke
3. The active transport of Ca2+ back into the SR during
relaxation
ATP must constantly be supplied for contractile
activity to continue
Skeletal Muscle Metabolism
Additional ATP is supplied by three pathways:
1. Creatine phosphate
Creatine phosphate + ADP Creatine + ATP
First source for supplying additional ATP
2. Oxidative phosphorylation
Takes place within the muscle mitochondria if sufficient O2 is present
Fueled by glucose and fatty acids
Relatively slow because involves many steps
3. Glycolysis
Synthesis ATP in the absence of O2
Uses large amounts of stored glycogen and produces lactic acid in
the process
Skeletal Muscle Metabolism
Types of Skeletal Muscle Fibres
Three types of muscle fibres are classified by:
The pathways they used for ATP synthesis
Oxidative
Glycolytic
The Speed of their contraction
Fast
Slow
1. Slow-oxidative (type I) fibres
2. Fast-oxidative (type IIa) fibres
3. Fast-glycolytic (type IIb) fibres
Types of Skeletal Muscle Fibres
Fast vs slow fibres
Fast fibres have higher myosin ATPase (ATP-splitting)
activity
ATP is split More rapidly
The rate at which energy is made available for cross-bridge cycling
is faster
Results in a fast twitch
Fast fibres are activated by large-diameter motor neurons
Slow fibres are activated by small-diameter motor neurons
Types of Skeletal Muscle Fibres
Oxidative vs glycolytic fibres
Oxidative fibres have a greater capacity to form ATP
More ATP is yielded from each nutrient molecule
processed → does not readily deplete energy stores
Does not result in lactic acid accumulation
More resistant to fatigue
• Oxidative fibres have a high myoglobin content →
red fibres
Types of Skeletal Muscle Fibres
Most skeletal muscles contain a
mixture of all three fibre types
A single motor unit always
contains one type or the other
The percentage of each type
determined by the type of
activity for which the muscle is
specialised
Muscle Hypertrophy
Enlargement (increase in diameter) of muscle
Total mass of muscle increases
Results from increased synthesis of actin and myosin
filaments in each muscle fibre
Occurs when the muscle undergoes regular bouts of
anaerobic, short-duration, high-intensity resistance
training
Muscle Atrophy
Muscle becomes smaller and weaker
Total mass of muscle decreases
Results from decrease of actin and myosin content
Disuse atrophy
Occurs when a muscle is not used for a long
period of time even though the nerve supply is
intact
Denervation atrophy
Occurs after the nerve supply to a muscle is lost
