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14/10/2011
Muscle
Dr Sarah Harney
Department of Physiology
[email protected]
• How is muscle tissue organised?
• How do muscles contract?
• How does muscle store/use energy?
• What changes occur in muscle with use/disuse?
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Functions of Muscle Contraction
• Controlled muscle contraction allows
– Purposeful movement of the whole body or parts
of the body
– Manipulation of external objects
– Propulsion of contents through various hollow
internal organs
– Emptying of contents of certain organs to external
environment
Chapter 8 Muscle Physiology
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Muscle Tissue
• Comprises largest group of tissues in body
• Three types of muscle
– Skeletal muscle
• Make up muscular system
– Cardiac muscle
• Found only in the heart
– Smooth muscle
• Appears throughout the body systems as components
of hollow organs and tubes
• Classified in two different ways
– Striated or unstriated
– Voluntary or involuntary
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3 Muscle Types
Categorization of Muscle
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How does skeletal muscle contract?
• Structure
• Changes in Protein arrangements
Structure of Skeletal Muscle
• Muscle consists a number of muscle fibers lying
parallel to one another and held together by
connective tissue
• Single skeletal muscle cell is known as a muscle
fiber
– Multinucleated
– Large, elongated, and cylindrically shaped
– Fibers usually extend entire length of muscle
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Structure of Skeletal Muscle
• Myofibrils
– Contractile elements of muscle fiber
– Regular arrangement of thick and thin filaments
• Thick filaments – myosin (protein)
• Thin filaments – actin (protein)
– Viewed microscopically myofibril displays
alternating dark (the A bands) and light bands
(the I bands) giving appearance of striations
Muscle fiber
myofibril
Chapter 8 Muscle Physiology
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
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14/10/2011
Structure of Skeletal Muscle
• Sarcomere
– Functional unit of skeletal muscle
– Found between two Z lines (connects thin filaments of two
adjoining sarcomeres)
– Regions of sarcomere
• A band
– Made up of thick filaments (Myosin) along with portions of thin
filaments that overlap on both ends of thick filaments
• I band
– Consists of remaining portion of thin filaments (Actin) that do
not project into A band
Structure of Skeletal Muscle
Sarcomere
Chapter 8 Muscle Physiology
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
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Changes in Banding Pattern During Shortening
Sliding filament model of contraction
Thick and thin filaments do not change length during contraction
but overlap to reduce sarcomere length
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A number of Proteins are Essential for Muscle Contraction
Thick filaments
• Myosin
Thin filaments
• Actin
• Troponin
• Tropomysin
Role of Calcium in Cross-Bridge Formation
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Cross bridge cycling requires Ca2+ release
from intracellular stores and ATP
Ca2+ released from intracellular stores binds to troponin, allowing actin
to interact with myosin
Adenosine triphosphate (ATP) is the energy source for all cells of the body.
Nutrients – glucose- are converted to ATP and energy is stored in the high energy
phosphate bonds of ATP. Breakdown of ATP to ADP releases energy which is used
by the cell
ATP
ADP + inorganic phosphate (Pi)
ATP binding to myosin is required for cross bridge detachment and priming for
subsequent cross-linking.
Following death, the absence of ATP prevents cross bridge detachment, causing
rigor mortis
Smooth muscle
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Smooth muscle
No z-lines, therefore actin is anchored to dense bodies, made of same protein as
z-lines in skeletal muscle
Cardiac Muscle
Chapter 8 Muscle Physiology
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
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14/10/2011
Smooth Muscles: Contrasted to Skeletal
Muscle
• Homeostatic role
– Control fluid
– Sphincters
• Tonic contractions
– Support tubes
– Move products
• Slow contractions
– Little fatigue
– Low O2 use
Figure 12-24: Duration of muscle contraction in
three types of muscle
Motor Unit Recruitment
• A single muscle is innervated by
multiple motor neurons
• Each motor neuron innervates a
number of muscle fibres, but
each muscle fibre receives input
from only one motor neuron
• The muscle fibres activated
simultaneously by the same
motor neuron are known as a
motor unit
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The synapse between motor neurons and skeletal muscle is
The Neuromuscular Junction (NMJ)
1. Action potential
propagated to motor neuron
axon terminal
2. Depolarization of voltagegated Ca2+ channels
3. Increase in Ca2+ triggers
release of Acetylcholine
4. Acetylcholine diffuses
across junction, binds to and
opens Ach receptor channels
5. Na+ enters muscle cell
motor end plate, depolarizing
the cell
Acetylcholine is the Neurotransmitter at the NMJ
Motor neuron endplates
on skeletal muscle
• Acetylcholine (Ach) is released by motor neuron axon terminals
• Binds to nicotinic Ach receptors on skeletal muscle tissue
• Depolarization (positive change in membrane potential) results in muscle
contraction
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Agents that block or modify activity at the NMJ
• ACh receptors are blocked by organophosphate poisons – used as pesticides
(malathion) or nerve gas (sarin)
• In the autoimmune disease myasthenia gravis, antibodies to the ACh receptors
block Ach binding, causing muscle weakness
• Botulinum toxin (Botox) blocks Ach release at the NMJ – can be fatal in
Botulism (due to inhibition of breathing) but is used clinically to relax muscles
in spasm and for cosmetic purposes
Motor Unit Recruitment
• Motor unit
– One motor neuron and the muscle fibers it innervates
• Number of muscle fibers varies among different motor units
• Number of muscle fibers per motor unit and number of motor
units per muscle vary widely
– Muscles that produce precise, delicate movements contain
fewer fibers per motor unit, e.g. fingers – 1 nerve to 1
muscle fibre, finely controlled movement
– Muscles performing powerful, coarsely controlled
movement have larger number of fibers per motor unit,
e.g. leg muscles -1 nerve to 2000 muscle fibres, large
increases in muscle tension
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Summation and Tetanus
•During a single stimulus, twitch, released Ca2+ allows cross-bridge formation and
muscle contraction
• Following initial stimulus Ca2+ is pumped back into intracellular stores
• Prolonged stimulation elevated intracellular Ca 2+, all cross bridges are formed and
the muscle reaches maximal tension, known as tetanus
Muscle Tension
• Tension is produced internally within muscle
• Tension must be transmitted to bone by means of connective
tissue and tendons before bone can be moved (series-elastic
component)
• Muscle typically attached to at least two different bones
across a joint:
Origin
End of muscle attached to more
stationary part of skeleton
Insertion
End of muscle attached to skeletal
part that moves
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Physics of Joint Movement
• Bones, muscles, and joints
interact to form lever systems
• Muscles: contraction force
– Isotonic: ‘constant
tension’, used for body
movements and moving
objects
– Isometric: ‘constant
length’, no movement,
used for maintaining
posture and for
supporting objects in a
fixed position
Muscle contraction
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Skeletal Muscle Metabolism
Alternative pathways for production of ATP
Muscle
glycogen
• Glycolysis can lead to the
formation of lactate during
conditons of limited O2 supply,
i.e. during high intensity activity
Glucose
Glycolysis
ATP
No O2 (anaerobic)
Lactate
Pyruvate
Oxidative
Phosphorylation
O2 (aerobic)
ATP
CO2
H2O
• Lactate accumulation causes
muscle burn during activity
• Oxidative phosphorylation
requires O2 and yields more ATP
but is relatively slow and is
utilised more during slower,
endurance activity
Chapter 8 Muscle Physiology
Human Physiology by Lauralee Sherwood ©2007 Brooks/Cole-Thomson Learning
Muscle cells can also store energy as creatine phosphate
• Cellular creatine phosphate stores are used
in the first minute of intense activity
Creatine phosphate + ADP
Creatine kinase
Creatine + ATP
• Creatine is obtained in dietary protein
• Creatine supplements are commonly used
by athletes, however the benefits are risks of
long-term use are not established
• Some evidence of liver/kidney problems, not
conclusive
• Supplements may be beneficial for patients
with muscular dystrophy, age-related muscle
wasting or diseases such as Parkinson’s
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Fast and Slow Muscle Fibre Types
Type I Slow twitch fibres
Type II Fast twitch fibres
(Type IIa and Type IIb, use different mechanisms for ATP generation)
Proportions of type I and type II fibres:
• vary between muscle types, e.g. more slow twitch fibres in muscles used for
low-intensity activity, such as the legs and more fast twitch fibres in muscles used
for fast movements, such as the biceps
• is genetically determined
Sprint athletes – more fast twitch fibres
Endurance athletes –
more slow twitch fibres
Muscle Fatigue
• Occurs when exercising muscle can no longer
respond to stimulation with same degree of
contractile activity
• Defense mechanism that protects muscle from
reaching point at which it can no longer produce
ATP
• Underlying causes of muscle fatigue are unclear,
most likely relate to build up of metabolic byproducts such as inorganic phosphate, lactate,
excess K+ or depletion of energy stores
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Central Fatigue
• Occurs when CNS no longer adequately activates
motor neurons supplying working muscles
• Often psychologically based
• Mechanisms involved in central fatigue are poorly
understood
Adaptive changes in Muscle
Hypertrophy
• High intensity resistance training results in increased
muscle mass, due to increased fast twitch fibres
• Increased synthesis of myosin and actin filaments
resulting in greater contractile strength
Sex differences in skeletal muscle mass:
42 % of body mass in males
36 % of body mass in females
• Testosterone and similar androgen
steroid hormones stimulate myosin and
actin synthesis
• Steroid abuse associated with many
cardiovascular, reproductive and
psychological side effects
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Adaptive changes in Muscle
Atrophy
• Reduced muscle mass associated with lack of use
• Can occur when nerve supply is intact but muscle not used e.g.
during recovery from a broken bone
• May result from loss of nerve stimulation following injury
• Electrical muscle stimulation (EMS)
may be useful in patients with chronic
illness or for recovering function after
stroke
• Some models of EMS developed by
NASA as astronauts suffer muscle
atrophy after long periods of zero
gravity
From: Sheffler and Chae,
Muscle and Nerve (2007) 35: 562-590
Reanimating Limbs After Disease
Richard B. Stein and Vivian Mushahwar
Review TRENDS in Neurosciences Vol.28 No.10 October 2005
Intact muscle not receiving input due to CNS disease
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Use of Electrical Muscle Stimulation after Spinal cord Injury
Figure 1 | Brain-controlled functional electrical
stimulation (FES) of muscle. a, Schematic shows
cortical cell activity converted to FES during
peripheral nerve block. b, Example of motor cortex
cell activity controlling FES of paralysed wrist
extensors. Extensor (red shading) and centre (grey
shading) wrist torque targets were randomly
presented. Monkeys learned to modulate smoothed
cell rate to control proportional muscle stimulation.
FES was delivered to muscles EDC and ED4,5 at 50
s21, with current proportional to cell rate above a
stimulation threshold (0.4mApps213[cell rate216 pps];
#10 mA). Here pps indicates pulses per second. c,
Histograms of cell rates while acquiring the extensor
and centre targets, illustrating cell activity used to
successfully control FES. Shading indicates target hold
period and horizontal line denotes baseline cell rate.
Moritz et al. (2008) Direct control of
paralysed muscles by cortical neurons.
Nature 456, 639-642
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