1. Muscles and Muscle Tissue
Chapter 9
Muscles and Muscle Tissue
J.F. Thompson, Ph.D. & J.R. Schiller, Ph.D. & G. Pitts, Ph.D.

2. 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. Thompson’s 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

5. 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

6. 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

7. 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.)

8. Sarcomere
The foundation of the muscle cell’s 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)

9. 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

10. Thick (Myosin) Myofilaments
Each thick filament contains many myosin units woven together

11. 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

12. 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

13. Regulation of Contraction & 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 neuron’s branches (axon)
motor end plate: the specialized region of the muscle cell plasma membrane adjacent to the axon terminal

14. 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

15. 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

16. 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)
axonal terminal
motor end plate

17. 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)

18. Generation of an Action Potential

19. Generation of an Action Potential

20. 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  

21. 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…

22. 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

23. 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

24. Calcium (Ca2+) off The “on-off switch”: allows myosin to bind to actin

25. 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

26. The Power Stroke & ATP
Cross bridge attachment. Myosin heads bind to actin
The working stroke. myosin changes shape (pulls actins toward M line); releases ADP + Pi
Cross bridge detachment. Myosin heads bind to a new ATP; releases actin

27. 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

28. 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

29. RATCHET EFFECT ANIMATION

30. 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
Ca2+ binds to troponin, causing tropomyosin to move out of its blocking position
Myosin forms cross bridges to actin, the power stroke occurs, filaments slide, muscle shortens
Calsequestrin and calmodulin help regulate Ca2+ levels inside muscle cells

31. 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

32. 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

33. 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.

34. Skeletal Muscle Motor Units
The Motor Unit = Motor Neuron + Muscle Fibers to which it connects (Synapses)  

35. 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

36. 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)        

37. 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

38. Muscle Twitchs
All or None Rule: all the muscle fibers of a motor unit contract all the way when stimulated

39. 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 muscle’s length

40. 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

41. Treppe: the staircase effect
“warming up” of a muscle fiber

42. Multiple Motor Unit Recruitment (Summation)
The stimulation of more motor units leads to a more forceful muscle contraction  

43. 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. 

44. 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

45. 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 % of Lo

46. Contraction of a Skeletal Muscle
Isometric Contraction: Muscle does not shorten
Tension increases

47. Contraction of a Skeletal Muscle
Isotonic Contraction: tension does not change
Muscle (length) shortens

48. 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

49. 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

50. Direct Phosphorylation – Creatine Phosphate System
CrP stored in cell
Allows for rapid ATP replenishment
Only a small amount available (10-30 seconds worth)

51. 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

52. 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 % of the needed ATP during these periods

53. Summary of Muscle Metabolism

54. 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

55. Factors Affecting the Force 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

56. 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

57. 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)

58. Force, Velocity, and Duration of Muscle Contraction

59. 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

60. 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  

61. Some extra slides for your review follow this slide.
End Chapter 9
Some extra slides for your review
follow this slide.

62. 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

63. 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

64. 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

65. 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

66. Developmental Aspects: Male and Female
There is a biological basis for greater strength in men than in women
Women’s skeletal muscle makes up 36% of their body mass
Men’s skeletal muscle makes up 42% of their body mass

67. 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

68. 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

69. End Chapter 9
End of review slides.