.

DR. REBECCA WONG

FACULTY OF MEDICINE
SEGI UNIVERSITY

Learning Outcomes

Discuss events that occur at the neuromuscular

junction leading to contraction and relaxation of
skeletal muscle fiber
Explain the sliding filament mechanisms of muscle
contraction
Describe the three ways in which muscle fibres make
ATP

Neuromuscular Junction (NMJ)

The neuromuscular junction is a connection between an

axon terminal and a muscle fiber where stimulation of the
muscle cell to contract occurs.
The neuromuscular junction consists of the plasma
membrane of the motor neuron axon terminal, the
synaptic cleft, and the motor endplate.
The motor endplate is part of the sarcolemma where
chemically regulated ion channels that respond to neural
stimulation are found.
Junctional folds increase the surface area at the motor
endplate.

Components of the NMJ

Synapse

Synaptic cleft

Chemical released by the initial cell

communicating with the second cell

Synaptic vesicles

Gap that separates the two cells

Neurotransmitter

Where communication occurs

between a somatic motor neuron and
a muscle fiber

Sacs suspended within the synaptic

end bulb containing molecules of the
neurotransmitter acetylcholine (Ach)

Motor end plate

The region of the muscle cell

membrane opposite the synaptic end
bulbs. Contain acetylcholine
receptors

http://users.bergen.org/dondew/bio/AnP/AnP1/An
P1Tri2/FIGS/AnPT2Fig06.html

Sequence of Events at the NMJ

Nerve impulses elicit a muscle action potential in the following way:

1) Release of acetylcholine

Nerve impulse arriving at the synaptic end bulbs causes many synaptic vesicles to
release ACh into the synaptic cleft

2) Activation of ACh receptors

Binding of ACh to the receptor on the motor end plate opens an ion channel
Allows flow of Na+ to the inside of the muscle cell

3) Production of muscle action potential

The inflow of Na+ makes the inside of the muscle fiber more positively charged
triggering a muscle action potential
The muscle action potential then propagates to the SR to release its stored Ca++

4) Termination of ACh activity

Ach effects last only briefly because it is rapidly broken down by

acetylcholinesterase (AChE)

Copyright 2009, John Wiley & Sons, Inc.

Some interesting facts

Botulinum toxin

Produced by Clostridium Botulinum

Blocks release of ACh from synaptic
vesicles
Results in muscle paralysis
May be found in improperly canned
foods
A tiny amount can cause death by
paralyzing respiratory muscles
Used as a medicine (Botox)
Strabismus (crossed eyes)
Blepharospasm (uncontrollable
blinking)
Spasms of the vocal cords that
interfere with speech
Cosmetic treatment to relax muscles
that cause facial wrinkles
Alleviate chronic back pain due to
muscle spasms in the lumbar region

Some interesting facts

Curare

A plant poison used by South American

Indians on arrows and blowgun darts
Causes muscle paralysis by blocking
ACh receptors inhibiting Na+ ion channels
Derivatives of curare are used during
surgery to relax skeletal muscles

Anticholinesterase

Slow actions of acetylcholinesterase and

removal of ACh
Can strengthen weak muscle contractions

E.g. : Neostigmine

Treatment for myasthenia gravis

Antidote for curare poisoning
Terminate the effects of curare after surgery

The Sliding Filament Mechanism

Myosin heads attach to and walk

along the thin filaments at both ends of
a sarcomere

Progressively pulling the thin filaments

toward the center of the sarcomere

Z discs come closer together and the

sarcomere shortens

Leading to shortening of the

entire muscle

LENGTHS OF INDIVIDUAL FILAMENTS

DONT CHANGE

Excitation-contraction coupling
increase in Ca2+ concentration in the muscle starts
contraction
A decrease in Ca2+ stops it
Action potentials causes Ca2+ to be released from the
SR into the muscle cell
Ca2+ binding of troponin moves tropomyosin away
from the myosin-binding sites on actin allowing crossbridges to form
The muscle cell membrane contains Ca2+ pumps to
return Ca2+ back to the SR quickly
Decreasing calcium ion levels
As the Ca2+ level in the cell drops, myosin-binding
sites are covered and the muscle relaxes
An

Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc.

The Contraction Cycle

The contraction cycle consists of 4 steps

1) ATP hydrolysis

Hydrolysis of ATP reorients and energizes the myosin head

2) Formation of cross-bridges

Myosin head attaches to the myosin-binding site on actin

3) Power stroke

During the power stroke the cross-bridge rotates, sliding the filaments

4) Detachment of myosin from actin

As the next ATP binds to the myosin head, the myosin head detaches from
actin
The contraction cycle repeats as long as ATP is available and the Ca++ level
is sufficiently high
Continuing cycles applies the force that shortens the sarcomere

Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc.

Copyright 2009, John Wiley & Sons, Inc.

Length-Tension relationship

The forcefulness of muscle

contraction depends on the
length of the sarcomeres

When a muscle fiber is

stretched there is less
overlap between the thick
and thin filaments and
tension (forcefulness) is
diminished

When a muscle fiber is

shortened the filaments are
compressed and fewer
myosin heads make
contact with thin filaments
and tension is diminished

Copyright 2009, John Wiley & Sons, Inc.

http://fau.pearlashes.com/anato
my/Chapter%2014/Chapter%20
14.htm

Muscle Metabolism
Production of ATP in Muscle Fibers
A huge amount of ATP is needed to:
Power the contraction cycle
Pump Ca2+ into the SR
The ATP inside muscle fibers will power contraction for only a few
seconds
ATP must be produced by the muscle fiber after reserves are
used up

Muscle fibers have three ways to produce ATP

1) From creatine phosphate
2) By anaerobic cellular respiration
3) By aerobic cellular respiration

Creatine Phosphate stores

Excess ATP is used to synthesize creatine phosphate
Energy-rich molecule
Creatine phosphate transfers its high energy
phosphate group to ADP regenerating new ATP
Creatine phosphate and ATP provide enough energy
for contraction for about 15 seconds

Copyright 2009, John Wiley & Sons, Inc.

Anaerobic Respiration
No oxygen required
When Creatine phosphate levels depleted
Glucose is derived from the blood and from glycogen stored in muscle
fibers
Glycolysis breaks down glucose into molecules of pyruvic acid and
produces two molecules of ATP
If sufficient oxygen is present, pyruvic acid formed by glycolysis enters
aerobic respiration pathways producing a large amount of ATP
If oxygen levels are low, anaerobic reactions convert pyruvic acid to
lactic acid which is carried away by the blood
Anaerobic respiration can provide enough energy for about 30 to 40
seconds of muscle activity

Copyright 2009, John Wiley & Sons, Inc.

Aerobic Respiration
Activity that lasts longer than half a minute depends on
aerobic respiration
Pyruvic acid entering the mitochondria is completely
oxidized generating:
ATP, carbon dioxide, water & heat
Each molecule of glucose yields about 36 molecules of
ATP
Muscle tissue has two sources of oxygen
1) Oxygen from hemoglobin in the blood
2) Oxygen released by myoglobin in the muscle cell
Aerobic respiration provides more than 90% of the
needed ATP in activities lasting more than 10 minutes

Copyright 2009, John Wiley & Sons, Inc.

Types of Fibers

Muscle fibers vary in their content of

myoglobin
Red muscle fibers
Have a high myoglobin content
Appear darker (dark meat in chicken
legs and thighs)
Contain more mitochondria
Supplied by more blood capillaries
White muscle fibers
Have a low content of myoglobin
Appear lighter (white meat in chicken
breasts)

Muscle Fibers

Muscle fibers contract at different speeds, and vary in how

quickly they fatigue
Muscle fibers are classified into three main types
1) Slow oxidative fibers
2) Fast oxidative-glycolytic fibers
3) Fast glycolytic fibers

Slow Oxidative (SO) Fibers

Smallest in diameter
Least powerful type of muscle fibers
Appear dark red (more myoglobin)
Generate ATP mainly by aerobic
cellular respiration
Have a slow speed of contraction

Twitch contractions last from 100 to 200

msec

Very resistant to fatigue

Capable of prolonged, sustained
contractions for many hours
Adapted for maintaining posture
and for aerobic, endurance-type
activities such as running a
marathon

Fast OxidativeGlycolytic (FOG) Fibers

Intermediate in diameter between

the other two types of fibers
Contain large amounts of
myoglobin and many blood
capillaries
Have a dark red appearance
Generate considerable ATP by
aerobic cellular respiration
Moderately high resistance to
fatigue
Generate some ATP by anaerobic
glycolysis
Speed of contraction faster

Twitch contractions last less than 100

msec

Contribute to activities such as

walking and sprinting

Fast Glycolytic (FG)Fibers

Largest in diameter
Generate the most powerful
contractions
Have low myoglobin content
Relatively few blood capillaries
Few mitochondria
Appear white in color
Generate ATP mainly by
glycolysis
Fibers contract strongly and
quickly
Fatigue quickly
Adapted for intense anaerobic
movements of short duration

Weight lifting or throwing a ball

Characteristics of Three Types of Skeletal Muscle Fibres

Type I
Slow-oxidative fibres

Type IIA
Fast-oxidative glycolytic
fibres

Type IIB
Fast-glycolytic fibres

Primary source of ATP

production

Oxidative
phosphorylation

Oxidative
phosphorylation

Glycolysis

Mitochondria

Many

Many

Few

Capillaries

Many

Many

Few

Myoglobin content

High (red muscle)

High (red muscle)

Low (white muscle)

Glycolytic enzyme activity Low

Intermediate

High

Glycogen content

Low

Intermediate

High

Rate of fatigue

Slow

Intermediate

Fast

Myosin-ATPase activity

Low

High

High

Contraction velocity

Slow

Fast

Fast

Fibre diameter

Small

Intermediate

Large

Motor unit size

Small

Intermediate

Large

Size of motor neuron

innervating fibre

Small

Intermediate

Large

http://classes.midlandstech.edu/carterp/Courses/bio210/chap09/lecture1.html

Distribution and Recruitment of

Different Types of Fibers

Most muscles are a mixture of all three types of muscle

fibers

Proportions vary, depending on the action of the muscle,

the person s training regimen, and genetic factors
Postural muscles of the neck, back, and legs have a high
proportion of SO fibers
Muscles of the shoulders and arms have a high proportion
of FG fibers
Leg muscles have large numbers of both SO and FOG
fibers

Ratios of fast glycolytic and slow oxidative fibers are

genetically determined

Exercise and Skeletal Muscle Tissue

Various types of exercises can induce changes in
muscle fibers

Aerobic exercise transforms some FG fibers into FOG

fibers
Endurance exercises do not increase muscle mass

Exercises that require short bursts of strength produce an

increase in the size of FG fibers
Muscle enlargement (hypertrophy) due to increased synthesis
of thick and thin filaments

Muscles during & after exercise

Muscle Fatigue
Inability of muscle to maintain force of contraction in
prolonged activity
Factors that contribute to muscle fatigue
Inadequate release of calcium ions from the SR
Depletion of creatine phosphate
Insufficient oxygen
Depletion of glycogen and other nutrients
Buildup of lactic acid and ADP
Failure of the motor neuron to release enough
acetylcholine

Muscles during & after exercise

Oxygen debt (recovery O2 uptake)
muscle activity breathing rate & blood flow to muscle

After exercise, heavy breathing continues and oxygen

consumption remains above the resting level
The added oxygen that is taken into the body after exercise is used
to restore muscle cells to the resting level in three ways
1) to convert lactic acid into glycogen
2) to synthesize creatine phosphate and ATP
3) to replace the oxygen removed from myoglobin

Further reading

Fundamentals of Anatomy & Physiology 7th Ed.

2006. Frederic H Martini. Pearson/Benjamin
Cummings.
Seeley's principles of anatomy & physiology 2009.
Philip Tate McGraw-Hill Higher Education
Principles of Anatomy and Physiology, 12th Ed.
2008. Gerard J. Tortora. Wiley.
Human anatomy & physiology 8th ed. 2006, Elaine
N. Marieb. Pearson/Benjamin Cummings.