LSB231-Physiology

y gy
 Muscle Physiology
y gy

Muscle tissue
A t
Anatomy off skeletal
k l t l muscles
l
The neuromuscular junction
Huxley’s sliding filament theory
Excitation
Contraction
M t units
Motor it
Types of skeletal muscle fibres
Other muscle types
 Muscle Physiology
y gy

Learning objectives
• Understand
U d t d th the anatomy
t off skeletal
k l t l muscle
l cells
ll
• Understand the function of:
¾The neuromuscular junction
¾Sliding filament theory of muscle contraction
¾Excitation / Contraction Coupling
¾Motor
M t units it
¾Types of skeletal muscle fibres
¾Other muscle types
 Muscle Tissue Types
yp

Converts chemical energy into mechanical energy.

Three basic types of muscle:

Skeletal striated voluntary control

Cardiac striated involuntary control
Smooth non-
non-striated involuntary control
 Muscle Tissue Types
yp

1. Cardiac 2. Skeletal 3. Smooth

• striated • striated • non-striated
• involuntary • voluntary • involuntary
 Muscle Tissue Functions

Muscle tissue facilitates;

• Locomotion & manipulation
• Body posture
• Stabilisation of joints
• Movement of substances internallyy
• Regulation of organ volume
• Generation of heat
 Root words: p
prefixes & suffixes

Root words:
• Muscle from the Latin for
little mouse “mus”

• ‘myo’ or ‘mys’ gk = muscle

• ‘sarco’ ‘sarx’ g
gk = flesh
• ‘plasm’ gk = form or mould
• ‘lemma’ = g gk sheath or husk
(refers to plasma membrane)
• ‘mere’ = segment
g
 Anatomyy of Skeletal Muscle

Levels of structure:
•Muscle
•Fascicle = (bundles)
•Fibre (cell)
•Myo
Myo--fibril: linked sarcomeres
•Thick and thin filaments
Thick: myosin
Thin: actin and others
•Sarcoplasmic reticulum
Stores and releases Ca2+
Skeletal Muscle (Cross-Section)
( )

•Endomysium = fine layer

of connective tissue
surrounding each muscle
fibre (cell)
•Perimysium
Perimysium = layer of
fibrous connective tissue
which surrounds each
fascicle
•Epimysium = layer of
dense irregular connective
tissue surrounds muscle
…sometimes blends with
deep facia between
neighbouring muscles
Anatomyy of Skeletal Muscle
Skeletal Muscle Fibres Stained

Alternating A (dark) and I (light) bands seen under

the microscope. “Striated”
 Muscle Fibres (Cells)
( )

Muscle cells:
• Are very large,
large 10-100μm Ø & packed with myofibrils

• Multinucleated,, formed from hundreds of embryonic

y cells

• Nuclei are pressed against sarcolemma (plasma membrane)

 Muscle Fibres (Cells)
( )

Muscle cells:
• Mitochondria are squeezed between myofibrils

• Myoglobin
y g used to transport
p O2 ((similar to haemoglobin)
g )

• Contain many glycosomes (granules of glycogen)

Myofibrils
y

Myofibrils:
•Run the whole length of
the muscle cell (up to
30cm long!)

•Are 1-2μm Ø

•Are composed of repeating

units called sarcomeres

•Give the muscle cell its

p ((striated))
striped
appearance
Sarcomeres

Sarcomeres:
•Are the individual
contractile units of muscle
fibres

•Mainly consist of two

different myofilaments

•Thick filaments – Myosin

•Thin filaments - Actin

Sarcomere:- Major
j Components
p
Thin Filament

Thin filaments:
•5-6nm in Ø, 1 μm long
•Constructed
Constructed from individual
G-actin proteins (g=globular)
•Two
Two chains of these molecules
are wound into an F-actin
helix (f=filamentous)
•Each F-actin is attached to
the Z-line.
Thin Filament

• The actin filament has a

number of other proteins
associated with it
• F actin
• tropomyosin
• troponins
• nebulin
• Troponin →(3 proteins)
• TnC binds Ca2+
• TnT binds Tropomyosin
• TnI binds Actin

• Tropomyosin changes shape

when troponin binds Ca2+
Thin Filament
•Complex between troponin,
troponin
tropomyosin + actin prevents
myosin
y from bindingg G actin active
site
•Active site binds myosin during
contraction not at rest
 Thick Filament

The thick filaments are composed of myosin proteins and

arranged such that the tails are linked in the middle
A titin protein runs through the centre of each thick filament
and traverses the sarcomere
Thick Filament

• Thick Filament
• 10-12nm
10 12nm diameter
• 1.6 microns long
• ~ 500 myosin molecules per
thick filament
• rod like tail
• 2 myosin polypeptide
chains
• wound around each other
• Heads contain actin and
ATP/ADP + Pi binding sites
Thick Filament
Titin:
• Very Large protein
– L
Largest polypeptide
l id
discovered
• Filament alignment
– attaches them to Z line
– stabilises filaments
• with nebulin
• helps resist stretch
– a stretchy protein
– allows muscle to spring
back into shape
– within core of thick
myosin filament
 Along the F-actin are attachment sites for the myosin heads.
The binding of the myosin head to its actin binding site forms a
crossbridge
 Muscle Contraction

Each sarcomere that makes upp the myofibril

y
shortens when the muscle cell (fibre) contracts
 Muscle Contraction

Each long myofibril contracts to shorten the muscle

cell
Neural Control

• CNS activates muscle

• somatic motor division
• motor neurons
• long axons
• myelinated
y
• > 1m
• nerve cell bodyy in
spinal cord or brain
• always
y excitatoryy
Neural Control
• Primary motor cortex
• Control over skeletal muscle
• Opposite side of the body
(connections cross over)
– Contralateral
• Motor cortex divided into
areas of the body
• Motor
M t h homunculus
l
• Stimulate - movement
– Area proportional to
precision and complexity
of motor skills
• Many other areas of brain
also involved
Excitation
The Neuromuscular Junction
 The Neuromuscular Junction
The neurotransmitter
is degraded by
acetylcholinesterase.

The membrane undergoes a local

action potential which then
spreads over the whole surface of
the muscle cell.
The muscle cell starts to contract.
Neuromuscular Junction vs Synapse
y p
Similarities
1. Both separated by a synaptic cleft.

2. Neurotransmitter is released when calcium gates open.

3 Both have specific receptors on the postsynaptic membrane.

3. membrane

4. Neurotransmitter opens gates in the postsynaptic membrane.

5. The membrane potential change which results is graded.

Neuromuscular Junction vs Synapse
y p
Differences
Diff
1. A synapse is a junction between two neurons.
A Neuromuscular Junction (NMJ) is between a neuron and a
skeletal muscle cell.

2. There is always an action potential in a postsynaptic membrane

when neurotransmitter is released in an NMJ.
A synapse needs summation of Excitatory Post synaptic Potentials.

3. A NMJ is always excitatory.

A synapse may be excitatory or inhibitory
 Muscle Contraction

An action potential spreads rapidly over the muscle cell from

the
h NMJ but
b there
h is
i a brief
b i f llatent period
i d (5 to 10 msecs))
before contraction occurs
 Excitation

B f
Before a muscle
l cell
ll can contract calcium
l i must b
be released
l d
into the cytoplasm
Components
p Needed For Excitation

The sarcolemma is the muscle cell membrane

Components
p Needed For Excitation

T-tubules are extensions of the muscle cell membrane deep

into the cytoplasm of the muscle cell.
They are filled with extracellular fluid.
Components
p Needed For Excitation

The sarcoplasmic
Th l i reticulum
ti l iis a network
t k off membranous
b
channels throughout the cytoplasm of the muscle cell.
Components
p Needed For Excitation

Junctional feet conduct an action potential from

the T-tubule to the sarcoplasmic reticulum
Components
p Needed For Excitation

Terminal
T i l cisternae
i t are partt off th
the
sarcoplasmic reticulum which stores calcium
Components
p Needed For Excitation

C l i
Calcium channels
h l llead
d ffrom th
the sarcoplasmic
l i reticulum
ti l iinto
t
the cytoplasm. They are normally closed.
Components
p Needed For Excitation

Calcium is continually being pumped from the

cytoplasm
l back
b k into theh sarcoplasmic
l reticulum.
l
This is an active transport process.
Excitation Process

• The action potential

spreads from the
NMJ all over the
sarcolemma.

• It spreads down into

each T
T-tubule
tubule.

• It spreads through
the junctional feet
into the
sarcoplasmic
l i
reticulum
Excitation Process

• The calcium
channels are voltage
gated and open.

• Calcium
C l i diffuses
diff
into the cytoplasm.

• Calcium binds to
troponin which
leads to the
attachment of
myosin
i hheads.
d
Excitation Process

• Myofibrils start to
contract.

• Calcium is pumped
outt off th
the
cytoplasm.

• Myosin binding sites

are covered and the
myofibrils relax.
 Biomechanics
o ec a cs

Tension = force generated by muscle on object.

object

Load = force (weight) exerted by object on muscle.

muscle

To lift an object (i.e. shorten the muscle).

Tension > Load
 Biomechanics
o ec a cs

Tension > Load length decreases concentric

load unchanged (isotonic)

Tension = Load length unchanged isometric

Tension < Load muscle stretches eccentric

actin myosin cross
actin-myosin
bridges provide brake.
Concentric ((isotonic)) contraction

The cross bridge cycling overcomes the

resistance and the muscle shortens
 The effect of load

As the load increases the distance the muscle

is able to contract decreases
 Isometric contraction

Crossbridges cycle but can not overcome the

resistance (weight)
The muscle does not shorten
 Eccentric contraction

The cross bridges act as a brake while

the muscle gradually lengthens
Eccentric contraction
 Strength
St e gt le
length
gt relationships
elat o s ps

Stretching a muscle too much results in a decreased force

generated
A Muscle Twitch
 A Muscle Twitch

A single action potential will cause a muscle to contract

briefly then relax
Muscle Twitch
w tc

• Muscle twitch has 3 phases

¾Latent Period – ECC is
occuring and muscle tension
is building.

¾Period of Contraction – X
bridges are active from onset
to peak of tension
development, lasts 10-100ms.

¾Period of Relaxation – lasts

10-100ms, initiated by re-
entry of Ca2+ to SR
Muscle Twitch
w tc

• Muscle twitch is rapid in

some muscles and slower in
others.
¾Rapid, short duration –
eyes

¾Slower,, longer
g duration-
Calf muscles
The
e effect
e ect oof multiple
ult ple st
stimulation
ulat o

• Repetitively stimulating the muscle results in a phenomemon

called wave summation
• Due to additional stimulus before muscle has completely
relaxed (repolarised)
• Due to ↑ Ca2+ release from SR
The
e effect
e ect oof multiple
ult ple st
stimulation
ulat o

• Unfused tetanus occurs when stimulus strength is held

constant but is applied repeatedly
• Relaxation time between twitches becomes shorter
• [Ca2+] in sarcoplasm increases further
• Degree of summation becomes greater
The
e effect
e ect oof multiple
ult ple st
stimulation
ulat o

• Fused tetanus occurs when stimulus frequency increases and

muscle tension increases until maximum tension is reached
• Relaxation disappears & contractions are fused
• Result – smooth, sustained contraction plateau
 Skeletal muscle ((motor units))

The
h combination
b off the
h motor nerve cell
ll (neuron) and
d all
ll
the muscle cells it innervates is known as a motor unit
Skeletal muscle ((motor units))

Motor units are the functional divisions of a muscle.

Each muscle cell in a unit contracts at the same time.
 Skeletal muscle ((motor units))

When an electrical impulse travels down the axon, all muscle

cells attached to the motor unit contract simultaneously
Skeletal muscle ((motor units))

Muscles
M l contain
t i many motor t units
it
Act as individual entities - contract as individual units.
 Skeletal muscle ((motor units))

Individual cells in a motor unit can be anywhere within a

muscle
 Motor unit recruitment

• Motor units are not all

ension

excited simultaneously
3 when a muscle is
uscle Te

recruited
motor unit 3 stimulated to contract
hole - Mu

2
1 recruited • While some motor units
recruited
motor unit 2 are contracting and
Wh

shortening within the

motor unit 1 muscle belly, others will
Time be relaxing and
lengthening
 Motor unit recruitment

More force is generated in a muscle by recruiting more motor

units
 Motor unit recruitment

Varying the number of activated motor units

• Size
Si P Principle
i i l - Smallest
S ll motor neurons are recruited
i d
first and deactivated last; opposite for large ones

• Rate Coding - Varying the rate at which each active

motor unit g
generates an action potential.
p

• Controlled by varying rate of action potentials in

corresponding
di motor
t neurons.
 Strength
g of motor units

The more fibres in a motor unit the stronger the unit

 Motor units – motor control

• FINE MOTOR CONTROL

• The motor units have a small number of
musclel cells.
ll
• e.g. in muscle moving the eyeball only
10 - 15 muscle cells in each motor unit

• GROSS MOTOR CONTROL

• The motor units have a large number of
muscle cells
• e.g. in
i th
the erector
t spinae
i muscles
l off th
the
back 1000 – 3000 muscle cells in each
motor unit
 Lets watch a movie of muscles in action
then discuss muscle energy requirements
 Muscle energy
gy & metabolism

• Muscle cells have about 4-6 sec of ATP reserves

• Creatine
C ti Ki Kinase regenerates
t ATP ffrom ADP & C
Creatine
ti
phosphate (CP) almost immediately following hydrolysis of
ATP to ADP + Pi during contraction
• Together ATP and CP stores fuel maximum power for 10-15 sec
Muscle energy
gy & metabolism
 Types
yp of muscle fibres

Muscle fibres can be classified according to…

• Size:
Si Ph
Physical
i l di
diameter
t

• Rate
R t off contraction:
t ti R
Rate
t off ATPase
ATP activity
ti it
• myosin and calcium/ATPase pump

• Major pathway used to produce ATP

• oxidative: via oxygen dependent processes in
mitochondria.
•gglycolytic:
y y via g
glycolysis
y y ((large
g store of g
glycogen).
y g )
 Types
yp of muscle fibres

Muscle fibres can be classified according to…

T
Type I.
I Small,
S ll Sl
Slow, O
Oxidative
id ti Fib
Fibres.

T
Type II . Mid-
IIa.
IIa Mid-size,
i F
Fast,
t Oxidative
O id ti Fib
Fibres.

T
Type IIb.. Large,
IIb L F
Fast,
t Glycolytic
Gl l ti Fibres.
Fib

• The larger the muscle fibre

fibre, the greater the force
generated.
• Due to greater total number of contracting
myofibrils.
Cross-section of skeletal muscle

Stained to show the slow twitch (type I) fibres

(dark blue, mitochondria)
Slow and fast-twitch muscles

• A single skeletal muscle is

made up of both major fibre
types:-
i.e. slow twitch (ST) and
fast twitch
t itch (FT)

• ST and FT fibres are grouped

into motor units.

• Motor units never have a

mixture of fibre types.
Slow and fast twitch muscles

On average muscles contain:- 50% ST and 50% FT

but the p
percentages
g do changeg in individual muscles
 Fast & slow-twitch fibre differences

• Speed at which the myosin head splits ATP

• Sarcoplasmic reticulum more developed in the fast twitch

fibre

• Fast twitch fibres have larger diameter axons

• Slow twitch motor units have 10 - 200 fibres whereas fast

twitch typically have 300 - 800 fibres

• Fast twitch motor units generate more force than slow twitch

• Fast twitch motor units fatigue more quickly than slow twitch
Slow twitch fibres
• They make up a slow
twitch motor unit

• These take about 110

milliseconds to reach
peakk tension
t i when h
excited

• Sometimes these are

called type I or slow
oxidative (SO) fibres

• They make up a slow

twitch motor unit
Fatigue due to lactic acid

A slow twitch (SO) fibre is fatigue resistant

It generates small amounts of lactic acid
Fast twitch fibres
• They make up a fast twitch
motor unit

• These take about 50

milliseconds to reach peak
tension when excited

• They can be further

subdivided into FTa, FTb,
and FTc fibres

• Sometimes these are called

type II fibres, Fast
Glycolytic(FG) and Fast
Oxidative/glycolytic (FOG)
Fast twitch motor units

• In general there are 300

to 800 muscle fibres in a
single motor unit

• In ggeneral fast twitch

motor units are stronger
than slow twitch ones

• Motor units are fast to

contract with high force
but fatigue easily
Fatigue
at gue due
ue to lact
lacticc ac
acid

A fast twitch (FG) fibre fatigues quickly

It generates most of the lactic acid
Fatigue
at gue due
ue to lact
lacticc ac
acid

A fast twitch (FOG) fibre fatigues gradually.

gradually
It generates lots of lactic acid.
 Motor unit recruitment

In general small motor units are recruited before larger ones

Muscle Tissue Types:
Types:-
C di Ti
Cardiac Tissue
 Muscle Tissue Types:
Types:-
C di Ti
Cardiac Tissue - Histology
Hi l
• Cardiac muscle cells are
joined together and function
as a syncytium
y y

• The striated appearance is

due to sarcomeres
d

• Have intercalated discs

Branching cardiac
fibres
Muscle Tissue Types:
Types:-
S
Smooth
h muscle
l
 Muscle Tissue Types:
Types:-
S
Smooth
h muscle
l - structure
• Spindle shaped

• The
Th actin
ti and
d myosin
i are nott
arranged into sarcomeres

• Roughly central nucleus

Muscle Tissue Types:
Types:-
S
Smooth
h muscle
l - histology
hi l
 Muscle Tissue Types:
Types:-
S
Smooth
h muscle
l - histology
hi l

Artery wall

Smooth
muscle
l
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