Excitable Cells (IV) Mechanism of Skeletal Muscle Contraction

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 Where communication occurs

between a somatic motor neuron and a muscle fiber

Synaptic cleft Gap that separates the two cells

Neurotransmitter Chemical released by the initial cell

communicating with the second cell

Synaptic vesicles 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

DON’T CHANGE

Excitation-contraction coupling

An 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 cross-bridges 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



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




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


http://fau.pearlashes.com/anato

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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


Anaerobic Respiration

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

No oxygen required When Creatine phosphate levels depleted


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


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 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

Muscle 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

Slow Oxidative (SO) 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 Oxidative–Glycolytic (FOG) 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

Fast Glycolytic (FG)Fibers

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

Ca++ sequestration Slow Fast Fast

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

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

Muscles during & after exercise

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.

Excitable Cells (IV) Mechanism of Skeletal Muscle Contraction

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