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3 Types of Muscle Tissue

1. Skeletal
2. Cardiac
3. Smooth
• Skeletal muscle
– attaches to bone, skin or fascia
– striated with light & dark bands visible with scope
– voluntary control of contraction & relaxation

• Cardiac muscle
– striated in appearance
– involuntary control
– autorhythmic because of built in pacemaker

• Smooth muscle
– attached to hair follicles in skin
– in walls of hollow organs - blood vessels & GI
– nonstriated in appearance
– involuntary
– autorhythmic

Functions of Muscle Tissue
• Producing body movements
• Stabilizing body positions
• Regulating organ volumes
– bands of smooth muscle called sphincters
• Movement of substances within the body
– blood, lymph, urine, air, food and fluids, sperm
• Producing heat
– involuntary contractions of skeletal muscle (shivering)

Properties of Muscle Tissue
• Excitability - respond to chemicals released from
nerve cells
• Conductivity - ability to propagate electrical
signals over membrane
• Contractility - ability to shorten and generate force
- 2 types of shortening: isometric and isotonic
• Extensibility - ability to be stretched without being
• Elasticity - ability to return to original shape after
being stretched
Skeletal Muscle - Connective Tissue
• Superficial fascia is loose connective tissue & fat
underlying the skin, path for BV & nerves
• Deep fascia = dense irregular connective tissue around
muscles with similar functions, isolates muscles from
body allowing movement
• Connective tissue components of the muscle include
– epimysium = surrounds the whole muscle
– perimysium = surrounds bundles (fascicles) of 10-100
muscle cells
– endomysium = separates individual muscle cells
• All these connective tissue layers extend beyond
the muscle belly to form the tendon
Connective Tissue Components

Nerve and Blood Supply
• Each skeletal muscle is supplied by a nerve,
artery and vein, and a rich capillary bed.
• Each motor neuron supplies multiple muscle cells
(neuromuscular junction = NMJ)
• Each muscle cell is supplied by one motor neuron
terminal branch and is in contact with one or two
– nerve fibers & capillaries are found in the
endomysium between individual cells

Fusion of Myoblasts into Muscle Fibers

• Every mature muscle cell develops from 100 myoblasts that fuse
together in the fetus. (multinucleated)
• Mature muscle cells can not divide
• Muscle growth is a result of cellular enlargement (hypertrophy) &
not cell division (hyperplasia)
• Satellite cells retain the ability to regenerate new muscle fibers.

Muscle Fiber = Myofiber

• Muscle cells are long, cylindrical & multinucleated

• Sarcolemma = muscle cell membrane
• Sarcoplasm filled with tiny threads called myofibrils &
myoglobin (red-colored, oxygen-binding protein)
Transverse Tubules

• T (transverse) tubules are invaginations of the

sarcolemma into the center of the cell
– filled with extracellular fluid
– carry muscle action potentials down into cell
• Mitochondria lie in rows throughout the cell
– near the muscle proteins that use ATP during contraction10-12
Myofibrils & Myofilaments

• Muscle fibers are filled with threads called myofibrils

encircled by SR (sarcoplasmic reticulum)
• Myofilaments (thick & thin filaments) are the
contractile proteins of muscle 10-13
Sarcoplasmic Reticulum (SR)

• System of tubular sacs similar to smooth ER in

nonmuscle cells
• Stores Ca+2 in a relaxed muscle
• Release of Ca+2 triggers muscle contraction
• Forms ‘triad’ with T-tubules 10-14
Atrophy and Hypertrophy
• Atrophy
– wasting away of muscles
– caused by disuse (disuse atrophy) or severing of the
nerve supply (denervation atrophy)
– the transition to connective tissue can not be reversed
• Hypertrophy
– increase in the diameter of muscle fibers, not number
– resulting from forceful, repetitive muscular activity
and an increase in myofibrils, SR & mitochondria

Filaments and the Sarcomere
• Thick and thin filaments overlap each other in
a pattern that creates striations (light I bands
and dark A bands)
• The I band region contains only thin filaments.
• They are arranged in compartments called
sarcomeres, separated by Z discs.
• In the overlap region, six thin filaments
surround each thick filament

Overlap of Thick & Thin Myofilaments
within a Myofibril

Dark(A) & light(I) bands visible with an electron microscope

Thick & Thin Myofilaments

• Supporting proteins (M line, titin and Z disc help

anchor the thick and thin filaments in place) 10-18
Exercise-Induced Muscle Damage
• Intense exercise does cause muscle damage
– electron micrographs reveal torn sarcolemmas,
damaged myofibrils and disrupted Z discs
– increased blood levels of myoglobin & creatine
phosphate found only inside muscle cells
• Delayed onset muscle soreness
– 12 to 48 hours after strenuous exercise
– stiffness, tenderness and swelling due to
microscopic cell damage

The Proteins of Muscle
• Myofibrils are built of 3 kinds of protein
– contractile proteins
• myosin and actin
– regulatory proteins which turn contraction on & off
• troponin and tropomyosin
– structural proteins which provide proper alignment,
elasticity and extensibility
• titin, myomesin, nebulin and dystrophin

The Proteins of Muscle - Myosin

• Thick filaments are composed of myosin

– each molecule resembles two golf clubs with twisted together
– myosin heads (cross bridges) extend toward the thin filaments
• Held in place by the M line proteins - myomesin.

The Proteins of Muscle - Actin

• Thin filaments are made of actin, troponin, & tropomyosin

• The myosin-binding site on each actin molecule is covered by
tropomyosin in relaxed muscle
• The thin filaments are held in place by Z lines. From one Z line to the
next is a sarcomere.

Structure of Actin and Myosin

The Proteins of Muscle - Titin

• Titin anchors thick filament to the M line and extends to the Z disc.
• Titan is filamentous, springy; maintains side-by-side orientation of
sliding filaments
• The portion of the molecule between the Z disc and the end of the
thick filament can stretch to 4 times its resting length and spring
back unharmed.
• Role in recovery of the muscle from being stretched, prevents
overextension, maintains the position of A band in the center of the
sarcomere. 10-25
Other Structural Proteins

• The M line (myomesin) connects to titin and adjacent thick filaments.

• Nebulin, an inelastic protein helps align the thin filaments.
• Dystrophin links thin filaments to integral sarcolemmal proteins and
transmits the tension generated to the tendon.

Components of Sarcomeres

Sliding Filament Model

• Actin myofilaments sliding over myosin to

shorten sarcomeres
– Actin and myosin do not change length
– Sarcomere shortening is responsible for skeletal
muscle contraction
• During relaxation, sarcomeres lengthen

Sliding Filament Mechanism Of Contraction
• Myosin cross bridges
pull on thin filaments
• Thin filaments slide
inward (toward M line)
• Z Discs come toward
each other
• Sarcomeres shorten.The
muscle fiber shortens. The
muscle shortens
• Notice : Thick & thin
filaments do not change in
Sarcomere Shortening

Sarcomere shortening

How Does Contraction Begin?
• Nerve impulse reaches an axon terminal &
synaptic vesicles release acetylcholine (ACh)
• ACh diffuses to receptors on the sarcolemma &
Na+ channels open, Na+ rushes into the cell
• A muscle action potential spreads over
sarcolemma and down into the transverse tubules
• SR releases Ca+2 into the sarcoplasm
• Ca+2 binds to troponin & causes troponin-
tropomyosin complex to move & reveal myosin
binding sites on actin - contraction cycle begins
Contraction Cycle
• Repeating sequence of events that cause the
thick & thin filaments to move past each other.
• 4 steps to contraction cycle
– ATP hydrolysis
– attachment of myosin to actin to form crossbridges
– power stroke
– detachment of myosin from actin
• Cycle keeps repeating as long as there is ATP
available & high Ca+2 level near thin filament

ATP and Myosin
• Myosin heads are activated by ATP
• Activated heads attach to actin & pull (power stroke)
• ADP is released.
• Thin filaments slide past the thick filaments
• ATP binds to myosin head & detaches it from actin
• All of these steps repeat over and over
– if ATP is available &
– Ca+2 level near the troponin-tropomyosin complex is high

Steps in the Contraction Cycle

Cross-Bridge Movement

Breakdown of ATP and Cross Bridge

Action Potentials and Muscle Contraction

Action potential along the T
tubules opens Ca channels on
the SR.
T-tubules and SR are physically
linked by a membrane protein –
which also functions as a Ca
channel. The ryanodine
receptor comes in contact with
T-tubule membrane proteins –
dihydropyridine (DHP)
receptors. DHPs function as
voltage sensors. Voltage
change alters the DHPs
conformation which opens the
ryanodine receptors
Action Potentials and Muscle Contrac

• Muscle action potential ceases
• Acetylcholinesterase (AChE) breaks down ACh
within the synaptic cleft
• Ca+2 release channels on the SR close
• Active transport pumps Ca2+ back into storage in
the sarcoplasmic reticulum
• Calcium-binding protein (calsequestrin) helps
hold Ca+2 in SR (Ca+2 concentration is 10,000 times
higher in SR than in cytosol)
• Tropomyosin-troponin complex recovers binding
site on the actin 10-41
Neuromuscular Junction (NMJ) or Synapse

• NMJ = myoneural junction

– end of axon nears the surface of a muscle fiber at its motor end plate region
(remain separated by synaptic cleft or gap)
Neuromuscular Junction (NMJ)

• Synapse or NMJ
– Presynaptic terminal
– Synaptic cleft
– Postsynaptic membrane or motor end-plate
• Synaptic vesicles
– Acetylcholine: Neurotransmitter
– Acetylcholinesterase: A degrading enzyme in synaptic cleft 10-43
Ion Channels

• Types
– Ligand-gated
• Example:
– Voltage-gated
• Open and close in
response to small
voltage changes across
plasma membrane

Structures of NMJ Region
• Synaptic end bulbs are swellings of
axon terminals

• End bulbs contain synaptic vesicles

filled with acetylcholine (ACh)

• Motor end plate membrane contains

30 million ACh receptors.

Function of Neuromuscular

Function of Neuromuscular Junction

Events Occurring After a Nerve Signal
• Arrival of nerve impulse at nerve terminal causes release of
ACh from synaptic vesicles
• ACh binds to receptors on muscle motor end plate opening the
gated ion channels so that Na+ can rush into the muscle cell
• Inside of muscle cell becomes more positive, triggering a
muscle action potential that travels over the cell and down the
T tubules
• The release of Ca+2 from the SR is triggered and the muscle cell
will shorten & generate force
• Acetylcholinesterase breaks down the ACh attached to the
receptors on the motor end plate so the muscle action potential
will cease and the muscle cell will relax.

Pharmacology of the NMJ
• Botulinum toxin blocks release of neurotransmitter at the
NMJ so muscle contraction can not occur
– bacteria found in improperly canned food
– death occurs from paralysis of the diaphragm
• Curare (plant poison used for arrows)
– causes muscle paralysis by blocking the ACh receptors
– used to relax muscle during surgery
• Neostigmine (anti-cholinesterase agent)
– blocks removal of ACh from receptors - strengthens weak
muscle contractions (as in myasthenia gravis)
– also an antidote for curare after surgery is finished

Excitation - Contraction Coupling

All the steps that occur from the muscle action potential reaching the T tubule to contraction of the muscle fiber.

Overview: From Start to Finish

• Nerve ending
• Neurotransmittor
• Muscle membrane
• Stored Ca+2
• Muscle proteins

Rigor Mortis
• Rigor mortis is a state of muscular rigidity that
begins 3-4 hours after death and lasts about 24
• After death, Ca+2 ions leak out of the SR and allow
myosin heads to bind to actin
• Since ATP synthesis has ceased, crossbridges
cannot detach from actin until proteolytic enzymes
begin to digest the decomposing cells.

Length of Muscle Fibers
• Optimal overlap of thick & thin filaments
– produces greatest number of crossbridges and the
greatest amount of tension
• Overstretching muscle (past optimal length)
– fewer cross bridges exist & less force is produced
• If muscle is overly shortened (less than optimal)
– fewer cross bridges exist & less force is produced
– thick filaments crumpled by Z discs
• Normally
– resting muscle length remains between 70 to 130% of
the optimum
Length Tension Curve
• Graph of Force of contraction
(Tension) versus Length of
• Optimal overlap at the top
of the graph
• When the cell is too stretched
little force is produced
• When the cell is too short, again
little force is produced

Muscle Metabolism
Production of ATP in Muscle Fibers
• Muscle uses ATP at a great rate when active
• Sarcoplasmic ATP only lasts for few seconds
• 3 sources of ATP production within muscle
– creatine phosphate
– anaerobic cellular respiration
– aerobic cellular respiration

Energy Sources
• ATP provides immediate energy for muscle
contractions from 3 sources
– Creatine phosphate
• During resting conditions stores energy to synthesize ATP
– Anaerobic respiration
• Occurs in absence of oxygen and results in breakdown of glucose
to yield ATP and lactic acid
– Aerobic respiration
• Requires oxygen and breaks down glucose to produce ATP,
carbon dioxide and water
• More efficient than anaerobic

Creatine Phosphate
• Excess ATP within resting muscle used to form creatine
• Creatine phosphate is 3-6
times more plentiful
than ATP within muscle
• Its quick breakdown
provides energy for
creation of ATP
• Sustains maximal contraction for 15 sec (used for 100
meter dash).
• Athletes tried creatine supplementation
– gain muscle mass but shut down bodies own synthesis (safety?)

Anaerobic Cellular Respiration
• ATP produced from glucose
breakdown into pyruvic acid
during glycolysis
– if no O2 present
• pyruvic converted to lactic acid
which diffuses into the blood
• Glycolysis can continue
anaerobically to provide ATP
for 30 to 40 seconds of
maximal activity (200 meter
Aerobic Cellular Respiration

• ATP for any activity lasting over 30 seconds

– if sufficient oxygen is available, pyruvic acid enters the
mitochondria to generate ATP, water and heat
– fatty acids and amino acids can also be used by the mitochondria
• Provides 90% of ATP energy if activity lasts more than 10
• Decreased capacity to work and reduced
efficiency of performance
• Types:
• Psychological
– Depends on emotional state of individual
• Muscular
– Results from ATP depletion
• Synaptic
– Occurs in NMJ due to lack of acetylcholine

Muscle Fatigue
• Inability to contract after prolonged activity
– central fatigue is feeling of tiredness and a
desire to stop (protective mechanism)
– depletion of creatine phosphate
– decline of Ca+2 within the sarcoplasm
• Factors that contribute to muscle fatigue
– insufficient oxygen or glycogen
– buildup of lactic acid and ADP, decrease in pH
– insufficient release of acetylcholine from motor
neurons, lack of Ca+2
Oxygen Consumption after Exercise
Oxygen Debt
• Muscle tissue has two sources of oxygen.
– diffuses in from the blood
– released by myoglobin inside muscle fibers
• Aerobic system requires O2 to produce ATP
needed for prolonged activity
– increased breathing effort during exercise
• Recovery oxygen uptake
– elevated oxygen use after exercise (oxygen debt)
– lactic acid is converted back to pyruvic acid
– elevated body temperature increases rate of all
metabolic reactions
The Motor Unit

• Motor unit = one somatic motor neuron & all the skeletal muscle cells
(fibers) it stimulates
– muscle fibers normally scattered throughout belly of muscle
– One nerve cell supplies on average 150 muscle cells that all contract in unison.
• Total strength of a contraction depends on how many motor units are activated &
how large the motor units are

Stimulus Strength and Muscle
• All-or-none law for muscle
– Contraction of equal force in
response to each action
• Sub-threshold stimulus
• Threshold stimulus
• Stronger than threshold
• Graded response for whole
– Strength of contractions range
from weak to strong depending
on stimulus strength (frequency
of action potentials)

Twitch Contraction

• Brief contraction of all fibers in a motor unit in response to

– single action potential in its motor neuron
– electrical stimulation of the neuron or muscle fibers
• Myogram = graph of a twitch contraction
– the action potential lasts 1-2 msec
– the twitch contraction lasts from 20 to 200 msec 10-66
Parts of a Twitch Contraction
• Latent Period – 2 msec
– Ca+2 is being released from SR
– slack is being removed from elastic components
• Contraction Period
– 10 to 100 msec
– filaments slide past each other
• Relaxation Period
– 10 to 100 msec
– active transport of Ca+2 into SR
• Refractory Period (very short)
– muscle can not respond and has lost its excitability
– 5 msec for skeletal & 300 msec for cardiac muscle 10-67
Wave Summation
‘Temporal Summation’
• If second stimulation is applied after the refractory period
but before complete muscle relaxation - second contraction
is stronger than first (Why?)

Complete and Incomplete Tetanus

• Unfused tetanus
– if stimulate at 20-30 times/second, there will be only partial
relaxation between stimuli
• Fused tetanus
– if stimulate at 80-100 times/second, a sustained contraction
with no relaxation between stimuli will result 10-70
Explanation of Summation & Tetanus

• Wave summation & both types of tetanus

result from Ca+2 remaining in the sarcoplasm
• Force of 2nd contraction is easily added to
the first, because the elastic elements
remain partially contracted and do not delay
the beginning of the next contraction

Motor Unit Recruitment
‘Spatial Summation’
• Motor units in a whole muscle fire asynchronously
– some fibers are active others are relaxed
– delays muscle fatigue so contraction can be sustained
• Produces smooth muscular contraction
– not series of jerky movements
• Precise movements require smaller contractions
– motor units must be smaller (fewer fibers/nerve)
• Large motor units are active when greater tension is
Multiple Motor Unit Summation

• A whole muscle contracts with a small or large force

depending on number of motor units stimulated to
• Graded response
• Occurs in whole
muscle rested for
prolonged period
• Each subsequent
contraction is stronger
than previous until all
equal after few stimuli
• Reasons?
Note that although each individual muscle fiber and each motor unit
respond in all-or-none fashion, the muscle as a whole responds in
graded fashion.

Types of Muscle Contractions
• Isometric (static): No change in length while tension
may change
– Postural muscles of body
• Isotonic (dynamic): Change in length with constant
– Concentric: Overcomes opposing resistance and muscle
– Eccentric: Tension maintained but muscle lengthens
– Isokinetic: Maximal tension during contraction at
constant speed over full range of motion
• Muscle tone: Constant tension by muscles for long
periods of time

Isotonic and Isometric Contraction

• Isotonic contractions = a load is moved

– concentric contraction = a muscle shortens to produce force and
– eccentric contractions = a muscle lengthens while maintaining
force (most likely to cause injury!)
• Isometric contraction = no movement occurs
– tension is generated without muscle shortening
– maintaining posture & supporting objects in a fixed position
Only lengthening contractions result in damaged fibers
control *

Injured fibers (% total)

* different from
zero (p<0.05)

Other Measures of Contraction-Induced Injury

immediate mechanical disruption observed by EM.
enzyme release from degenerating muscle fibers
in human beings, subjective reports of muscle soreness
in the absence of fatigue, a decrease in the development
of force Koh & Brooks (2001)
Am J Physiol 281:R155-R161.
Muscle Tone

• Involuntary contraction of a small number of motor units

(alternately active and inactive in a constantly shifting
– keeps muscles firm even though relaxed
– does not produce movement
• Essential for maintaining posture (head upright)
• Important in maintaining blood pressure
– tone of smooth muscles in walls of blood vessels

Size Principle
of motor unit recruitment
The smallest motor units are always recruited first,
and recruitment proceeds with successively larger
motor units as more force is needed by the muscle.
Smallest motor units are recruited first because they
have the smallest neuronal somas (cell bodies),
which require less stimulation to fire action
potentials. In addition, small motor units have
smaller muscle fibers, which generate the least
amount of force.
• Active versus passive tension
Passive = the tension in the muscle present before
Active = the tension developed due to the
• Velocity of muscle shortening decreases with
increased load – at maximal load, the velocity is zero =
isometric contraction

• Sarcomeres are organized in ‘series’ and in ‘parallel’.

At the level of sarcomere organization, how would you
increase the tension? Amount of shortening?
Figure 6-9 Relation of muscle length to tension in the
muscle both before and during muscle contraction.
Downloaded from: StudentConsult (on 10 February 2006 03:56 PM)
© 2005 Elsevier
Figure 6-10 Relation of load to velocity of contraction in
a skeletal muscle with a cross section of 1 square
centimeter and a length of 8 centimeters.
Downloaded from: StudentConsult (on 10 February 2006 03:56 PM)
© 2005 Elsevier
Power output: the most physiologically relevant
marker of performance

Power = work / time

= force x distance / time
= force x velocity

Peak power obtained at intermediate loads and

intermediate velocities. Figure from Berne and Levy, Physiology
Mosby—Year Book, Inc.,10-83
Variations in Skeletal Muscle Fibers
• Myoglobin, mitochondria and capillaries
– red muscle fibers
• more myoglobin, an oxygen-storing reddish pigment
• more capillaries and mitochondria
– white muscle fibers
• less myoglobin and fewer capillaries give fibers their pale
• Contraction and relaxation speeds vary
– how fast myosin ATPase hydrolyzes ATP
• Resistance to fatigue
– different metabolic reactions used to generate ATP
Slow and Fast Fibers
• Slow-twitch
– Contract more slowly, smaller in diameter, better blood
supply, more mitochondria, more fatigue-resistant than
• Fast-twitch
– Respond rapidly to nervous stimulation, contain myosin
to break down ATP more rapidly, less blood supply,
fewer and smaller mitochondria than slow-twitch
• Distribution
– Most muscles have both, but proportion varies for each
• Effects of exercise
– Hypertrophies: Increases in muscle size
– Atrophies: Decreases in muscle size

Classification of Muscle Fibers

• Type I, slow oxidative (slow-twitch)

– red in color (lots of mitochondria, myoglobin & blood vessels)
– prolonged, sustained contractions for maintaining posture
• Type IIb, fast oxidative-glycolytic (fast-twitch)
– “pink” in color (lots of mitochondria, myoglobin & blood vessels)
– split ATP at very fast rate; used for walking and sprinting
• Type IIa, fast glycolytic (fast-twitch)
– white in color (few mitochondria & BV, low myoglobin)
– anaerobic movements for short duration; used for weight-lifting

Shortening velocity dependent on ATPase activity
Different myosin heavy chains (MHCs) have different ATPase activities.
There are at least 7 separate skeletal muscle MHC genes…arranged in series
on chromosome 17.
Two cardiac MHC genes located in tandem on chromosome 14.
The slow β cardiac MHC is the predominant gene expressed in slow fibers
of mammals.

Goldspink (1999) J Anat 10-87

Physiological profiles of motor units:
all fibers in a motor unit
are of the same fiber type
Slow motor units contain slow fibers:
• Myosin with long cycle time and
therefore uses ATP at a slow rate. FG
• Many mitochondria, so large capacity to
replenish ATP.
• Economical maintenance of force during
isometric contractions and efficient
performance of repetitive slow isotonic SO
Fast motor units contain fast fibers:
• Myosin with rapid cycling rates.
• For higher power or when isometric
force produced by slow motor units is
• Type FOG fibers are fast and adapted
for producing sustained power.
• Type FG fibers are faster, but non-
oxidative and fatigue rapidly.
Modified from Burke and Tsairis, Ann NY Acad Sci 228:145-159, 1974. 10-88
type I IIb IIa
Color red pink white
Speed of contraction slow fast fast
Max force generated low intermed high
Fiber diameter small intermed large
Motor unit size small intermed large
Resistance to fatigue high intermed low
Capillaries many many few
Mb content high high low
Mitochondria many many few
Glycogen low intermed high
Myosin-ATPase low high high
Oxidative phosphoryl’n high high low
Anaerobic glycolysis low intermed high
Sensitivity to hypoxia high intermed low
Fiber Types within a Whole Muscle
• Most muscles contain a mixture of all three fiber
• Proportions vary with the usual action of the
– neck, back and leg muscles have a higher proportion
of postural, slow oxidative fibers
– shoulder and arm muscles have a higher proportion
of fast glycolytic fibers
• All fibers of any one motor unit are same.
• Different types of fibers are recruited as needed.
Endurance training
Little hypertrophy but major biochemical adaptations within
muscle fibers.
Increased numbers of mitochondria; concentration and activities of
oxidative enzymes (e.g. succinate dehydrogenase, see below).

Succinate dehy-
drogenase (SDH)
Low activity light
High activity dark

Control 12-weeks
treadmill running 10-91
Images courtesy of John Faulkner and Timothy White
Strength training
Early gains in strength appear to be predominantly
due to neural factors…optimizing recruitment

Long term gains almost solely the result of

hypertrophy i.e. increased size.

(Compare the changes in strength vs endurance


Disuse causes atrophy - USE IT OR LOSE IT!
Individual fiber atrophy (loss of myofibrils) with no loss in fibers.

Effect more pronounced in Type II (fast) fibers.

“Completely reversible” (in young healthy individuals).

ATPase activity:

Type I (slow) fibers - light

Fast Type II (fast) fibers – dark
- (II) (staining is reversed)
- (I)

Control Prolonged
bed rest 10-93
Images courtesy of John Faulkner
Anabolic Steroids
• Similar to testosterone
• Increases muscle size, strength, and endurance
• Many very serious side effects
– liver cancer
– kidney damage
– heart disease
– mood swings “-roid rage”
– facial hair & voice deepening in females
– atrophy of testicles & baldness in males

Regulation of Contraction
• Regulation of contraction due to
– nerve signals from somatic and autonomic nervous
– changes in local conditions (pH, O2, CO2, temperature &
ionic concentrations)
– hormones (epinephrine - relaxes muscle in airways &
some blood vessels)
• Stress-relaxation response
– when stretched, initially contracts & then tension
decreases to what is needed
– stretch hollow organs as they fill & yet pressure
remains fairly constant
– when emptied, muscle rebounds & walls firm up
Regeneration of Muscle
• Skeletal muscle fibers cannot divide after 1st year
– growth is enlargement of existing cells
– repair
• satellite cells & bone marrow produce some new cells
• if not enough numbers - fibrosis occurs (most often)
• Cardiac muscle fibers cannot divide or regenerate
– all healing is done by fibrosis (scar formation)
• Smooth muscle fibers (regeneration is possible)
– cells can grow in size (hypertrophy)
– some cells (uterus) can divide (hyperplasia)
– new fibers can form from stem cells in BV walls

Effects of Aging on Skeletal
• Reduced muscle mass
• Increased time for muscle to contract in
response to nervous stimuli
• Reduced stamina
• Increased recovery time
• Loss of muscle fibers
• Decreased density of capillaries in muscle

Aging and Muscle Tissue
• Skeletal muscle starts to be replaced by fat
beginning at 30
– “use it or lose it”
• Slowing of reflexes & decrease in maximal
• Change in fiber type to slow oxidative fibers may
be due to lack of use or may be result of aging

Performance Declines
Declines with
with Aging
-- despite
despite maintenance
maintenance of
of physical
physical activity
Performance (% of peak)



Basketball (rebounds/game)

10 20 30 40 50 60
Age (years)
D.H. Moore (1975) Nature 253:264-265.
NBA Register, 1992-1993 Edition
Number of motor units declines during aging
- extensor digitorum brevis muscle of human beings


Individual fiber atrophy

(which may be at least
partially preventable and
reversible through exercise).

Loss of fibers
(which as yet appears

Campbell et al., (1973) J Neurol Neurosurg Psych 36:74-182.

Motor unit
unit remodeling
remodeling with
with aging
Central Muscle



• Fewer motor units

• More fibers/motor unit
Muscle injury may play a role in the development of
atrophy with aging.

• Muscles in old animals are more susceptible to contraction-

induced injury than those in young or adult animals.

• Muscles in old animals show delayed and impaired recovery

following contraction-induced injury.

• Following severe injury, muscles in old animals display

prolonged, possibly irreversible, structural and functional

Degeneration-regeneration not necessary to provide muscles
protection from contraction-induced injury
Force deficit (% control)

60 non-trained 60

Injured fibers (% total)

trained passive
50 trained isometric 50
40 * * * different from non- 40
-trained (p<0.05)
30 30
20 20
* 10
Koh & Brooks (2001)
0 0 Am J Physiol 281:R155-R161.
Force deficit Injured fibers

• Despite the increase in susceptibility to injury with aging,

and the decreased ability to recover, muscles in old
animals (humans?) can be conditioned for protection
from injury.
• Maintenance of conditioned fibers, particularly in muscles
of elderly people, may prevent inadvertent damage during
contractions. 10-103
Myasthenia Gravis
• Progressive autoimmune disorder that blocks the
ACh receptors at the neuromuscular junction
• The more receptors are damaged the weaker the
• More common in women 20 to 40 with possible link
to thymus gland tumors
• Begins with double vision & swallowing difficulties
& progresses to paralysis of respiratory muscles
• Treatment includes steroids that reduce antibodies
that bind to ACh receptors and inhibitors of
Muscular Dystrophies
• Inherited, muscle-destroying diseases
• Sarcolemma tears during muscle contraction
• Mutated gene is on X chromosome so problem is with males
almost exclusively
• Appears by age 5 in males and by 12 may be unable to walk
• Degeneration of individual muscle fibers produces atrophy of the
skeletal muscle
• Gene therapy is hoped for with the most common form =
Duchenne muscular dystrophy

Muscular Dystrophy:
A frequently fatal disease of muscle deterioration
• Muscular dystrophies have in the past been classified based on subjective and sometimes
subtle differences in clinical presentation, such as age of onset, involvement of particular
muscles, rate of progression of pathology, mode of inheritance.

• Since the discovery of dystrophin, numerous genetic disease loci have been linked to protein
products and to cellular phenotypes, generating models for studying the pathogenesis of the

• Proteins localized in the nucleus, cytosol, cytoskeleton, sarcolemma, and ECM.

Cohn and Campbell (2000) Muscle Nerve 23:1459-1471.

Dystrophin function:
transmission of force to extracellular matrix

DGC (dystroglycan

dystroglycan (α and
β )
sarcoglycans (α , β ,
γ ,δ )
syntrophins (α , β 1)
dystrobrevins (α , β )
(Some components of
laminin-α 2 (merosin)
the dystrophin glycoprotein
complex are relatively
recent discoveries, so one
cannot assume that all
players are yet known.)

Cohn and Campbell (2000) Muscle Nerve10-107

Abnormal Contractions
• Spasm = involuntary contraction of single
• Cramp = a painful spasm
• Tic = involuntary twitching of muscles that
are normally under voluntary control -
eyelid or facial muscles
• Tremor = rhythmic, involuntary contraction
of opposing muscle groups
• Fasciculation = involuntary, brief twitch of
a motor unit visible under the skin
Muscle Attachment Sites:
Origin and Insertion

• Skeletal muscles shorten & pull on the bones they are attached to
• Origin is the bone that does not move when muscle shortens
(normally proximal)
• Insertion is the movable bone (some 2 joint muscles)
• Fleshy portion of the muscle in between attachment sites = belly
Lever Systems and Leverage
• Muscle acts on rigid rods (bone)
that move around a
fixed point called a fulcrum
• Resistance is weight of body
part & perhaps an object
• Effort or load is work done
by muscle contraction
• Mechanical advantage
– the muscle whose attachment is farther from the joint will
produce the most force
– the muscle attaching closer to the joint has the greater range
of motion and the faster the speed it can produce
First - Class Lever
Fulcrum is between force and resistance
• May or may not produce mechanical
advantage depending on location of
effort & resistance
– if effort is further from fulcrum than
resistance, then a strong resistance can be
– (+) Need small tension to balance weight
– (-) Limitations are how far a load can be
moved and how heavy a load can be
• Head resting on vertebral column
– weight of face is the resistance
– joint between skull & atlas is fulcrum
– posterior neck muscles provide effort

Second - Class Lever
Resistance is between fulcrum and effort
• Similar to a wheelbarrow
• (+) Always produce mechanical
advantage (muscle tension needed
is less than the resistance)
– Resistance is always closer to
fulcrum than the effort
• (-) Sacrifice speed for force
• (-) Sacrifice distance a load can be
moved (it is less than the distance a
muscle shortens)
• Raising up on your toes
– resistance is body weight
– fulcrum is ball of foot
– effort is contraction of calf
muscles which pull heel up off of
Third - Class Lever
Force is between fulcrum and resistance
• Most common levers in the body
• (-) Always produce a mechanical
(muscle tension needed is greater
than the resistance)
– effort is always closer to fulcrum
than resistance
• (+) Favors speed and range of
motion over force
• Flexor muscles at the elbow
– resistance is weight in hand
– fulcrum is elbow joint
– effort is contraction of biceps
brachii muscle
Coordination Within Muscle Groups
• Most movement is the result of several muscle
working at the same time
• Most muscles are arranged in opposing pairs at
– prime mover or agonist contracts to cause the desired
– antagonist stretches and yields to prime mover
– synergists contract to stabilize nearby joints
– fixators stabilize the origin of the prime mover
• scapula held steady so deltoid can raise arm