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
neuron initiates an action potential in the
muscle fibres
2. Muscle action potential travels down T
tubule
3. Causes SR to release Ca2+ into
sarcoplasm
4. Ca2+ binds to troponin, exposing actin’s
cross-bridge binding sites
5. Myosin head binds to active site, form
cross-bride, moves and produces power
stroke
6. Actin slides in, muscle fibre contracts
resulting in contraction of whole
muscle
7. ADP and Pi are released after the
power stroke is complete
8. New ATP binds to myosin head;
detachment of the cross bridge
9. Cross-bridge action continues while
Ca2+ is present
10. When action potential stops, Ca2+
pumped back to SR
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