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. Some Muscle Terminology
Myology: the scientific study of muscle
muscle fibers = muscle cells
myo, mys & sarco: word roots referring to muscle

3. Three Types of Muscle Skeletal, cardiac, and smooth muscle differ in:
Microscopic anatomy
Location
Regulation by the endocrine system and the nervous system

4. Characteristics of Skeletal Muscle
Attached primarily to bones
Voluntary (conscious) control (usually)
Contracts quickly, tires easily (fatigable)
Allows for wide range of forces to be generated

5. Skeletal Muscle Cells Long, cylindrical cells Striated (banded)
Multinucleate

6. Characteristics of Cardiac Muscle
Forms most of heart wall (myocardium)
Involuntary (unconscious)
Autorhythmicity (contracts without external stimuli)
Fast contraction, non-fatigable
Beats at constant rhythm that can be modified by neural and hormonal signals

7. Cardiac Muscle Cells Branched cells
Uninucleate (may occasionally be binucleate)
Striated
Intercalated discs

8. Characteristics of Smooth Muscle
Found in the walls of hollow internal structures (digestive, respiratory, reproductive tracts, blood vessels)
Arrector pili, pupil of the eye, etc.
Involuntary (unconscious)
Long, slow contractions, non-fatigable

9. Smooth Muscle Cells
Nonstriated = smooth
Uninucleate

10. 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

11. 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

12. Connective Tissue Wrappings of Skeletal Muscle Tissue
Superficial Fascia: "hypodermis"
Deep Fascia: lines body walls & extremities; binds muscle together, separating them into functional groups
Epimysium: wraps an entire muscle
Perimysium: subdivides each muscle into fascicles, bundles of muscle fibers
Endomysium: wraps individual muscle fibers

13. Nerve and Blood Supply
Each muscle fiber is supplied by a branch of a motor nerve
Each muscle is supplied by its own arteries and veins
Blood vessels branch profusely to provide each muscle fiber with a direct blood supply

14. Attachments (to bone)
Origin: the part of a muscle attached to the stationary bone (relative to a particular motion)
Insertion: the part of a muscle attached to the bone that moves (relative to a particular motion)
Attachments are extensions of connective tissue sheaths beyond a muscle, attaching it to other structures
Direct attachment: epimysium fused to periosteum

15. Attachment Structure
Indirect attachment: connective tissue wrappings gathered into a tendon or aponeurosis which attaches to an origin or insertion on bone
Tendon: cord (of dense regular connective tissue)
Aponeurosis: sheet (of dense regular connective tissue)

16. Microscopic Anatomy of A Skeletal Muscle Fiber
Muscle fibers (cells): long, cylindrical, and multinucleate (individual muscle cells fuse during embryonic development)
Sarcolemma: the cell membrane of a muscle fiber
Sarcoplasm: the cytoplasm of a muscle fiber, rich in oxygen-storing myoglobin protein

17. Myofibrils of A Skeletal Muscle Fiber
Myofibrils: bundles of contractile protein filaments (myofilaments) arranged in parallel, fill most of the cytoplasm of each muscle fiber; 100’s to 1000’s per cell
Sarcomeres: the repeating unit of contraction in each myofibril

18. Organelles of A Skeletal Muscle Fiber
Mitochondria: provide the ATP required for contraction
Sarcoplasmic reticulum (smooth ER): stores Ca2+ ions which serve as second messengers for contraction
changed

19. Striations/Sarcomeres
Z discs (lines): the boundary between sarcomeres; proteins anchor the thin filaments; bisects each I band
A (anisotropic) band: overlap of thick (myosin) filaments & thin filaments
I (isotropic) band: thin (actin) filaments only
H zone: thick filaments only
M line: proteins anchor the adjacent thick filaments

20. 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.)

21. Sarcomeres
Components of the muscle fiber with myofilaments arranged into contractile units
The functional unit of striated muscle contraction
Produce the visible banding pattern (striations)
The myofilaments between two successive z discs

22. Summary of Muscle Structure

23. 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

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

25. 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

26. 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

27. Regulation of Contraction & The Neuromuscular Junction
Where motor neurons communicate with the muscle fibers
Composed of an axon terminal & motor end plate
Axon terminal: 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

28. 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

29. The Neuromuscular Junction:
Neurotransmitter: the chemical that travels across the synapse, i.e., acetylcholine, ACh)  
Acetylcholine (ACh) receptors: integral membrane proteins which bind ACh  

30. Generation of an Action Potential (Excitation)
Binding of 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

31. 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)

32. 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  

33. Excitation-Contraction Coupling
The action potential (excitation) travels over the sarcolemma, including T-tubules
DHP receptors serve as voltage sensors on the T-tubules and cause ryanodine receptors on the SR to open and release Ca2+ ions
And now, for the interactions between calcium and the sarcomere…

34. 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

35. 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

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

37. Calcium Movements Inside Muscle Fibers
Action potential causes 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

38. The Power Stroke & ATP Cross bridge attachment. myosin binds to actin
The working stroke. myosin changes shape (pulls actin toward it); releases ADP + Pi
Cross bridge detachment. myosin binds to new ATP; releases actin

39. The Power Stroke & ATP
4. "Cocking" of the myosin head. ATP hydrolyzed (split) to ADP + Pi; provides potential energy for the next stroke

40. The “Ratchet Effect”
Repeat steps 1-4: The “ratchet action” repeats the process, shortening the sarcomeres and myofibrils, until Ca2+ ions are removed from the sarcoplasm or the ATP supply is exhausted
Power
Stroke
Attach
Repeat
Release

41. RATCHET EFFECT ANIMATION

42. Excitation-Contraction Coupling
The action potential (excitation) travels over the sarcolemma, including T-tubules
DHP receptors serve as voltage sensors on the T-tubules and cause ryanodine receptors on the SR to open 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

43. 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

44. 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+ released in response to action potential delivered by motor neuron
Ca2+ ATPase pumps Ca2+ ions back into the SR

45. 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

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

47. 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

48. 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)        

49. Myogram Latent period: delay between stimulus and response
Contraction phase: tension or shortening occurs  
Relaxation phase: relaxation or lengthening  

50. Muscle Twitches
All or none rule: All the muscle fibers of a motor unit contract all the way when stimulated

51. 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

52. 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

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

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

55. The Size Principle
As stimulus intensity increases, motor units leads with larger fibers are recruited  

56. 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

57. 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

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

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

60. 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 no movement
e.g., neck, back and leg muscles
maintain posture

61. Muscle Metabolism Energy availability
Not much ATP is available at any given moment
ATP is needed for cross bridges and Ca2+ 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

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

63. 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

64. 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

65. Summary of Muscle Metabolism

66. 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

67. Factors Affecting the Force of Contraction
Number of muscle fibers contracting (recruitment)
2. Size of the muscle
Frequency of stimulation
Degree of muscle stretch when the contraction begins

68. 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)

69. Force, Velocity, and Duration of Muscle Contraction

70. Smooth Muscle Tissue
When the longitudinal layer contracts, the organ dilates and contracts
When the circular layer contracts, the organ elongates

71. 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

72. Contraction of Smooth Muscle
Some smooth muscle cells:
Act as pacemakers and set the contractile pace for whole sheets of muscle
Are self-excitatory and depolarize without external stimuli
Whole sheets of smooth muscle exhibit slow, synchronized contraction
They contract in unison, reflecting their electrical coupling with gap junctions
Action potentials are transmitted from cell to cell

73. Smooth Muscle Tissue Contracts under the influence of:
Autonomic nerves
Hormones
Local factors

74. 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

75. 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

76. 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

77. 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

78. 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

79. 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

80. Homeostatic Imbalances
Muscular dystrophy – group of inherited muscle-destroying diseases where muscles enlarge due to fat and connective tissue deposits, but muscle fibers atrophy.

81. 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  

82. End Chapter 9

83. Cardiac Muscle Tissue
Striated
Unicellular
Branched
Intercalated discs

84. Intercalated Discs Desmosomes Gap junctions connect cells
Electrical synapses
Excitation spreads rapidly

85. Smooth Muscle
Composed of spindle-shaped fibers with a diameter of 2-10 m and lengths of several hundred m
Lack the coarse connective tissue sheaths of skeletal muscle, but have fine endomysium
Organized into two layers (longitudinal and circular) of closely apposed fibers
Found in walls of hollow organs (except the heart)
Have essentially the same contractile mechanisms as skeletal muscle

86. Smooth Muscle Tissue No striations (no sarcomeres) Uninucleate
Spindle-shaped
Involuntary
May be autorhythmic
May have gap junctions

87. 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