Muscles and Muscle Tissue

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Chapter 9

• Muscles and Muscle Tissue

• J.F. Thompson, Ph.D. J.R. Schiller, Ph.D. G.
  Pitts, Ph.D.

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Muscles and Muscle Tissues

• Use the extra PPTs and audio PPTs to review
  muscle anatomy
• CH 9 Skeletal Muscle Histology
• CH 9 Skeletal Muscle Development
• CH 9 Cardiac Muscle Histology
• CH 9 Smooth Muscle Tissue

At Dr. Thompsons website
3
Some Muscle Terminology

• Myology the scientific study of muscle
• muscle fibers muscle cells
• myo, mys sarco word roots referring to muscle

4
Three Types of Muscle

• Skeletal, cardiac, and smooth muscle differ in
• Microscopic anatomy
• Location
• Regulation by the endocrine system and the
  nervous system

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Functions of Muscle Tissue

• Motion external (walking, running, talking,
  looking) and internal (heartbeat, blood pressure,
  digestion, elimination) body part movements
• Posture maintain body posture
• Stabilization stabilize joints muscles have
  tone even at rest
• Thermogenesis generating heat by normal
  contractions and by shivering

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Functional Characteristics

• Excitability (irritability)
• the ability to receive and respond to a stimulus
  (chemical signal molecules)
• Contractility
• ability of muscle tissue to shorten
• Extensibility
• the ability to be stretched without damage
• most muscles are arranged in functionally
  opposing pairs as one contracts, the other
  relaxes, which permits the relaxing muscle to be
  stretched back
• Elasticity
• the ability to return to its original shape
• Conductivity (impulse transmission)
• the ability to conduct excitation over length of
  muscle

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Myofibrils Sarcomeres -Myofilaments

• Thin filaments actin (plus some tropomyosin
  troponin)
• Thick filaments myosin
• Elastic filaments titin (connectin) attaches
  myosin to the Z discs (very high mol. wt.)

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Sarcomere

• The foundation of the muscle cells contractile
  organelle, myofibril
• The functional unit of striated muscle
  contraction
• The myofilaments between two adjacent Z discs
• The regular geometric arrangement of the actin
  and myosin produces the visible banding pattern
  (striations)

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Myosin Protein

• Rod-like tail with two heads
• Each head contains ATPase and an actin-binding
  site point to the Z line
• Tails point to the M line
• Splitting ATP releases energy which causes the
  head to ratchet and pull on actin fibers

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Thick (Myosin) Myofilaments

• Each thick filament contains many myosin units
  woven together

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Thin (Actin) Myofilaments

• Two G actin strands are arranged into helical
  strands
• Each G actin has a binding site for myosin
• Two tropomyosin filaments spiral around the actin
  strands
• Troponin regulatory proteins (switch molecules)
  may bind to actin and tropomyosin have Ca2
  binding sites

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Muscle Fiber Triads

• Triads 2 terminal cisternae 1 T tubule
• Sarcoplasmic reticulum (SER) modified smooth ER,
  stores Ca2 ions
• Terminal cisternae large flattened sacs of the
  SER
• Transverse (T) tubules inward folding of the
  sarcolemma

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Regulation of Contraction The Neuromuscular
Junction

• The Neuromuscular Junction
• where motor neurons communicate with the muscle
  fibers
• composed of an axon terminal, a synapse and a
  motor end plate
• axon terminal the end of the motor neurons
  branches (axon)
• motor end plate the specialized region of the
  muscle cell plasma membrane adjacent to the axon
  terminal

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The Neuromuscular Junction

• Synapse point of communication is a small gap  
  
• Synaptic cleft the space between axon terminal
  motor end plate  
• Synaptic vesicles membrane-enclosed sacs in the
  axon terminals containing the neurotransmitter

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The Neuromuscular Junction

• Neurotransmitter the chemical signal molecule
  that diffuses across the synapse, i.e.,
  acetylcholine, ACh)  
• Acetylcholine (ACh) receptors integral membrane
  proteins which bind ACh

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Generation of an Action Potential (Excitation)

• Binding of the neurotransmitter (ACh) causes the
  ligand-gated Na channels to open
• Opening of the Na channels depolarizes the
  sarcolemma (cell membrane)

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Generation of an Action Potential

• Initial depolarization causes adjacent
  voltage-gated Na channels to open Na ions flow
  in, beginning an action potential
• Action potential a large transient
  depolarization of the membrane potential
• transmitted over the entire sarcolemma (and down
  the T tubules)

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Generation of an Action Potential
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Generation of an Action Potential
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Generation of an Action Potential

• Repolarization the return to polarization due to
  the closing voltage-gated Na channels and the
  opening of voltage gated K channels  
• Refractory period the time during membrane
  repolarization when the muscle fiber cannot
  respond to a new stimulus (a few milliseconds)
•  
• All-or-none response once an action potential is
  initiated it results in a complete contraction of
  the muscle cell  

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Excitation-Contraction Coupling  

• The action potential (excitation) travels over
  the sarcolemma, including T-tubules
• Voltage sensors on the T-tubules cause
  corresponding SR receptors to open gated channels
  and release Ca2 ions
• And now, for the interactions between calcium and
  the sarcomere

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The Sliding Filament Model of Muscle Contraction

• Thin and thick filaments slide past each other to
  shorten each sarcomere and, thus, each myofibril
• The cumulative effect is to shorten the muscle

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http//www.lab.anhb.uwa.edu.au/mb140/CorePages/Mus
cle/Muscle.htmSKELETAL

• This simulation of the sliding filament model can
  also be viewed on line at the web site below
  along with additional information on muscle
  tissue

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Calcium (Ca2)

• The on-off switch allows myosin to bind to
  actin

off
on
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Calcium Movements Inside Muscle Fibers

• An action potential causes the release of Ca2
  ions (from the cisternae of the SR)
• Ca2 combines with troponin, causing a change in
  the position of tropomyosin, allowing actin to
  bind to myosin and be pulled (slide)
• Ca2 pumps on the SR remove calcium ions from the
  sarcoplasm when the stimulus ends

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The Power Stroke ATP

1. Cross bridge attachment. Myosin heads bind to
   actin
2. The working stroke. myosin changes shape (pulls
   actins toward M line) releases ADP Pi
3. Cross bridge detachment. Myosin heads bind to a
   new ATP releases actin

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The Power Stroke ATP

• 4. "Cocking" of the myosin head. ATP is
  hydrolyzed (split) to ADP Pi this provides
  potential energy for the next stroke

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The Ratchet Effect

• Repeat steps 1-4 The ratchet action repeats
  the process, shortening all the sarcomeres and
  the myofibrils, until Ca2 ions are removed from
  the sarcoplasm or the ATP supply is exhausted

Power Stroke
Attach
Repeat
Release
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RATCHET EFFECT ANIMATION

• http//www.sci.sdsu.edu/movies/actin_myosin_gif.ht
  ml

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Excitation-Contraction Coupling  

1. The action potential (excitation) travels over
   the sarcolemma, including T-tubules
2. Voltage sensors on the T-tubules cause
   corresponding SR receptors to open gated channels
   and release Ca2 ions
3. Ca2 binds to troponin, causing tropomyosin to
   move out of its blocking position
4. Myosin forms cross bridges to actin, the power
   stroke occurs, filaments slide, muscle shortens
5. Calsequestrin and calmodulin help regulate Ca2
   levels inside muscle cells

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Destruction of Acetylcholine  

• Acetylcholinesterase an enzyme that rapidly
  breaks down acetylcholine is located in the
  neuromuscular junction 
• Prevents continuous excitation (generation of
  more action potentials)  
• Many drugs and diseases interfere with events in
  the neuromuscular junction  
• Myasthenia gravis loss of function at ACh
  receptors (autoimmune disease?)  
• Curare (poison arrow toxin) binds irreversibly
  to and blocks the ACh receptors

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MUSCLE CONTRACTION

• One power stroke shortens a muscle about 1
• Normal muscle contraction shortens a muscle by
  about 35
• cross bridge (ratchet effect) cycle repeats
• continue repeating power strokes, continue
  pulling
• increasing overlap of fibers Z lines come
  together
• about half the myosin molecules are attached at
  any time
• Cross bridges are maintained until Ca2 levels
  decrease
• Ca2 is released in response to the action
  potential delivered by the motor neuron
• Ca2 ATPase pumps Ca2 ions back into the SR,
  using more ATP

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RIGOR MORTIS IN DEATH

• Ca2 ions leak from SR causing binding of actin
  and myosin and some contraction of the muscles
• Lasts 24 hours, then enzymatic tissue
  disintegration eliminates it in another 12 hours

This suicide victim used a shotgun to kill
himself when it was removed, his arms retained
this posture.
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Skeletal Muscle Motor Units

• The Motor Unit Motor Neuron Muscle Fibers to
  which it connects (Synapses)  

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Skeletal Muscle Motor Units

• The size of Motor Units varies
• Small - two muscle fibers/unit (larynx, eyes)
• Large hundreds to thousands/unit (biceps,
  gastrocnemius, lower back muscles)
• The individual muscle cells/fibers of each unit
  are spread throughout the muscle for smooth
  efficient operation of the muscle as a whole

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The Myogram

• Myogram a recording of muscle contraction
• Stimulus nerve impulse or electrical charge
• Twitch a single contraction of all the muscle
  fibers in a motor unit (one nerve signal)      
   

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Myogram

• 1. latent period delay between stimulus and
  response  
• 2. contraction phase tension or shortening
  occurs  
• 3. relaxation phase relaxation or lengthening  
  
• refractory period time interval after excitation
  when muscle will not respond to a new stimulus

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Muscle Twitchs

• All or None Rule all the muscle fibers of a
  motor unit contract all the way when stimulated

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Graded Muscle Responses

• Force of muscle contraction varies depending on
  need. How much tension is needed?
• Twitch does not provide much force
• Contraction force can be altered in 3 ways
• 1. changing the frequency of stimulation
  (temporal summation)
• 2. changing the stimulus strength (recruitment)
• 3. changing the muscles length

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Temporal Summation

• Temporal (wave) summation contractions repeated
  before complete relaxation, leads to
  progressively stronger contractions
• unfused (incomplete) tetanus frequency of
  stimulation allows only incomplete relaxation  
• fused (complete) tetanus frequency of
  stimulation allows no relaxation

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Treppe the staircase effect

• warming up of a muscle fiber

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Multiple Motor Unit Recruitment (Summation)

• The stimulation of more motor units leads to a
  more forceful muscle contraction  

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The Size Principle

• As greater force is required, the nervous
  system will stimulate more motor units, and motor
  units with larger fibers and larger numbers of
  fibers to achieve the desired strength of
  contraction. 

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Stretch Length-Tension Relationship

• Stretch (sarcomere length) determines the number
  of cross bridges
• extensive overlap of actin with myosin less
  tension
• optimal overlap of actin with myosin most
  tension
• reduced overlap of actin with myosin less
  tension
• Optimal overlap most cross bridges available for
  the power stroke and least structural interference

more resistance
most cross bridges/least resistance
fewest cross bridges
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Stretch Length-Tension Relationship

• Optimal length - Lo
• maximum number of cross bridges
• no overlap of actin fibers from opposite ends of
  the sarcomere
• normal working muscle range from 70 - 130 of Lo

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Contraction of a Skeletal Muscle

• Isometric Contraction Muscle does not shorten
• Tension increases

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Contraction of a Skeletal Muscle

• Isotonic Contraction tension does not change
• Muscle (length) shortens

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Muscle Tone

• Regular small contractions caused by spinal
  reflexes
• Respond to tendon stretch receptor sensory input
• Activate different motor units over time
• Provide constant tension development
• muscles are firm
• but do not shorten
• e.g., neck, back and leg muscles
• maintain posture

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Muscle Metabolism

• Energy availability
• Not much ATP is available at any given moment
• ATP is needed for cross bridges and Ca removal
• Maintaining ATP levels is vital for continued
  activity
• Three ways to replenish ATP
• 1. Creatine Phosphate energy storage system
• 2. Anaerobic Glycolysis -- Lactic Acid system
• 3. Aerobic Respiration

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Direct Phosphorylation Creatine Phosphate
System

• CrP stored in cell
• Allows for rapid ATP replenishment
• Only a small amount available (10-30 seconds
  worth)

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Anaerobic Glycolysis Lactic Acid System

• Anaerobic system - no O2 required
• Very inefficient, does not create much ATP
• Only useful in short term situations (30 sec - 1
  min)
• Produces lactic acid as a by-product

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Aerobic System

• Uses oxygen for ATP production
• Oxygen comes from the RBCs in the blood and the
  myoglobin storage depot
• Uses many substrates carbohydrates, lipids,
  proteins
• Good for long term exercise
• May provide 90-100 of the needed ATP during
  these periods

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Summary of Muscle Metabolism
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Oxygen Debt

• The amount of oxygen needed to restore muscle
  tissue (and the body) to the pre-exercise state
• Muscle O2, ATP, creatine phosphate, and glycogen
  levels, and a normal pH must be restored after
  any vigorous exercise
• Circulating lactic acid is converted/recycled
  back to glucose by the liver

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Factors Affecting theForce of Contraction

• Number of muscle fibers contracting (recruitment)
• Size of the muscle
• Frequency of stimulation
• Degree of muscle stretch when the contraction
  begins
• Series elastic elements

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Series Elastic Elements

• All of the noncontractile structures of a muscle
• Connective tissue coverings and tendons
• Elastic elements of sarcomeres
• Internal load force generated by myofibrils on
  the series elastic elements
• External load force generated by series elastic
  elements on load

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Muscle Fiber Type Speed of Contraction

• Slow oxidative fibers contract slowly, have slow
  acting myosin ATPases, and are fatigue resistant
  (red)
• Fast oxidative fibers contract quickly, have fast
  myosin ATPases, and have moderate resistance to
  fatigue
• Fast glycolytic fibers contract quickly, have
  fast myosin ATPases, and are easily fatigued
  (white)

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Force, Velocity, and Duration of Muscle
Contraction
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Homeostatic Imbalances

• The muscular dystrophies (MD) are a group of more
  than 30 genetic diseases characterized by
  progressive weakness and degeneration of the
  skeletal muscles that control movement.
• Some forms of MD are seen in infancy or
  childhood, while others may not appear until
  middle age or later.
• The disorders differ in terms of
• the distribution and extent of muscle weakness
• (some forms of MD also affect cardiac muscle)
• age of onset
• rate of progression
• pattern of inheritance

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Homeostatic Imbalances

• Duchenne Muscular Dystrophy
• Inherited lack of functional gene for formation
  of a protein, dystrophin, that helps maintain the
  integrity of the sarcolemma
• Onset in early childhood, victims rarely live to
  adulthood  

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End Chapter 9

• Some extra slides for your review
• follow this slide.

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Smooth Muscle Contractions

• Peristalsis alternating contractions and
  relaxations of smooth muscles that squeeze
  substances through the lumen of hollow organs
• Segmentation contractions and relaxations of
  smooth muscles that mix substances in the lumen
  of hollow organs

Peristalsis Animation
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Developmental Aspects of the Muscular System

• Muscle tissue develops from embryonic mesoderm
  called myoblasts (except the muscles of the iris
  of the eye and the arrector pili muscles in the
  skin)
• Multinucleated skeletal muscles form by fusion of
  myoblasts
• The growth factor agrin stimulates the clustering
  of ACh receptors at newly forming motor end
  plates
• As muscles are brought under the control of the
  somatic nervous system, the numbers of fast and
  slow fibers are also determined
• Cardiac and smooth muscle myoblasts do not fuse
  but develop gap junctions at an early embryonic
  stage

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Regeneration of Muscle Tissue

• Cardiac and skeletal muscle become amitotic, but
  can lengthen and thicken
• Myoblast-like satellite cells show very limited
  regenerative ability
• Satellite (stem) cells can fuse to form new
  skeletal muscle fibers
• Cardiac cells lack satellite cells
• Smooth muscle has good regenerative ability

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Developmental Aspects After Birth

• Muscular development reflects neuromuscular
  coordination
• Development occurs head-to-toe, and
  proximal-to-distal
• Peak natural neural control of muscles is
  achieved by midadolescence
• Athletics and training can improve neuromuscular
  control

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Developmental Aspects Male and Female

• There is a biological basis for greater strength
  in men than in women
• Womens skeletal muscle makes up 36 of their
  body mass
• Mens skeletal muscle makes up 42 of their body
  mass

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Developmental Aspects Male and Female

• These differences are due primarily to the male
  sex hormone testosterone
• With more muscle mass, men are generally stronger
  than women
• Body strength per unit muscle mass, however, is
  the same in both sexes

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Developmental Aspects Age Related

• With age, connective tissue increases and muscle
  fibers decrease
• Muscles become stringier and more sinewy
• By age 80, 50 of muscle mass is lost
  (sarcopenia)
• Regular exercise reverses sarcopenia
• Aging of the cardiovascular system affects every
  organ in the body
• Atherosclerosis may block distal arteries,
  leading to intermittent claudication and causing
  severe pain in leg muscles

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End Chapter 9

• End of review slides.