1. Muscle Three types of muscle: smooth cardiac skeletal
All muscles require ATP to produce movement. Thus, muscles are chemotransducers

2. Skeletal Muscle Muscle organization Muscle innervation
Architecture and structure
Excitation-contraction
Fiber type characteristics
Training adaptations
Exam 1 (Feb 8)

3. Skeletal muscle organization
Connective tissue layers
Epimysium
Perimeysium
Endomysium

5. Muscle fiber covering Sarcolemma Plasma membrane has basement membrane
membrane receptors
ion channels
integrins
satellite cells
multinuclei

7. Effect on force output and shortening velocity
Muscle Architecture
Effect on force output and shortening velocity

8. Muscle Architecture Muscle architecture
Muscles in which the fibers are parallel to the line of force, such as the biceps, can contract very quickly, but at a sacrifice of not being able to develop as much force as muscles, such as the vastus lateralis, in which the fibers are arranged at an angle (pennation) to the line of force. These muscles cannot contract as quickly, however, they can develop more force. Thus, muscles are designed to fulfill a particular function such as for force and power, or to be able to contract quickly.

9. Muscle Architecture
Parallel
Unipennation
Multipennation

10. Pennation: Effect on Physiological Cross-sectional Area (PCSA)
Greater PCSA when fiber is at angle to line of force B A A

11. Pennation: Effect on Force and Shortening Distance/Velocity
Fiber B
Fiber A
Equal number of sarcomeres in both examples, but Fiber A has longer fiber and smaller PSFA than Fiber B, which allows for greater shortening distance/velocity at sacrifice of force.

12. Identify which muscles are best suited for force; for speed

13. Muscle Architecture
quadriceps and planter flexors designed for force production
larger pennation angles
large PCSAs
hamstrings and dorsiflexors designed for velocity
smaller pennation angles
intermediate PCSAs

14. Muscle Architecture Summary Muscles designed to fit purpose of joint
Muscles designed for velocity have longer fiber length and small pennation angle
Muscles designed for force have shorter fiber length and larger pennation angle

15. Review questions
Describe the difference between a muscle with a fusiform architecture and one with a uni- or multipennate architecture. Identify a muscle for each type of architecture.
Discuss how muscle architecture affects force output and shortening velocity.  Provide a general explanation as to why some muscles are designed more for rapid shortening velocity (e.g. hamstrings) or higher force output (e.g. quadriceps muscles).

16. Motoneurons, neuromuscular junctions, motor units
Muscle Innervation
Motoneurons, neuromuscular junctions, motor units

17. Motoneurons
muscle fibers innervated by large (alpha) myelinated nerves
motoneurons originate from spinal cord
nerve ending ends at neuromuscular junction
motor unit composed of motor neuron and all the fibers it innervates

19. Action Potential depolarization – influx of Na+
repolarization – efflux of K+
refractory period – hyperpolarization
threshold level – minimal stimulus required to elicit response
muscle and nerve follow “all or nothing principle”

20. Na+ channel Na+-K+ exchange pump K+ channel intracellular +20 -20 -40
-20
-40
-60
-80
Membrane potential (mV)
Time (ms) K+ K+ K+
Na+
Na+ K+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
Na+
channel
Na+-K+
exchange pump K+
channel
ATPase K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+
ADP K+ K+ K+ K+
Na+ Pi
Na+
Na+
Na+
intracellular
ATP

21. Neuromuscular Junction
ACh (acetylcholine) is the neurotransmitter at all neuromuscular junctions. Not shown is how ACh is rapidly removed following release; otherwise, the action potentials would not cease causing continual contraction. Many drugs, including nerve gases, work at these locations by either blocking the neurotransmitter receptors or inhibiting the removal of the neurotransmitter.

22. Top graph is force output from a hand-grip dynamometer and the lower graph is the EMG activity of the forearm flexors during the hand grip.

23. Electromyography (EMG)
Bicep EMG activity of six arm curls. Be able to interpret the EMG activities so as to describe the changes in weight of the dumbbells. Also, note the differences in EMG activity between the concentric and eccentric phases.
Describe the relative weights being lifted

24. Review questions Define the motor unit.
Describe the events that occur as an action potential approaches the nerve terminal.
Explain the purpose of acetylcholinesterase and the consequences of its absence.
A common agent found in flea powders is a low dose of an antiacetylcholinesterase inhibitor. Explain the effects that the flea powder would have on fleas.
Explain the interpretation of an EMG tracing.

25. Sarcomere Structure

26. Skeletal Muscle Structure

27. Cross-Sectional View of Skeletal Muscle (X40)

28. Skeletal Muscle Structure
sarcomeres (smallest functional unit) are linked end-to-end to form myofibrils
myofibrils are bunched to form fibers
sarcomeres are composed of thick and thin filaments

29. Scanning EM 1 4 2
1) Z disk; 2) length of sarcomere; 3) length of thick filaments; 4) intramuscular triglyceride droplet; 5) M-line (a cytoskeletal structure to hold the thick filaments in place. The numerous small black dots are glycogen molecule complexes. 5 3

30. Thick Filament composed of numerous myosin protein strands
flexible “heads” protrude outward all around filament (except center)
myosin heads attach to “active” sites on actin (thin) filament
myosin heads contain ATPase to break down ATP

31. Myosin filament
Two myosin filaments wind around each other in a double-helix fashion. Also, there are two flexible points on the myosin filaments; one is indicated in the top figure, and a second is at the junction of the myosin head and the S2 segment. This allows the myosin filament to “reach out” and bind to an actin molecule as well as for the myosin head to swivel during the “power stroke” movement of contraction. Within each myosin head is a cleft where the ATP binds. Also within the cleft is the myosin ATPase.

32. Myosin Filament
Pairs of myosin heads protrude every 60º around the circumference of the thick filament.

33. Thin Filament Composed of three proteins
actin - two protein strands twisted around each other, contain “active sites”
tropomyosin - thin strand laying in actin groove that covers active sites
troponin - attached to actin and tropomyosin strands; has strong affinity for Ca2+

34. Thin Filament
The actin filament is actually two strands of polymerized actin molecules that are twisted together in a double helix manner. The active site to which the myosin heads attach are “covered” by the tropomyosin filaments that sit in the groove of the double actin filament. The troponin complex attaches to both the actin and tropomyosin filaments, and when Ca2+ binds to it, the troponin undergoes a conformational change that causes the tropomyosin filament to be lifted away from the active sites.

35. Cytoskeleton (structural) proteins
M-band – located in middle of thick filament; provides structural support to myosin filaments; contains creatine kinase (CK)
Titan –connects myosin filament to Z-disk; stabilizes myosin in middle of sarcomere.
Z-disk –thin filaments attachment; composed of several cytoskeletal proteins

36. Actin-myosin orientation
Notice the cross-sectional arrangement in how each thick filament is surrounded by six thin filaments, and each thin filament is within reach of three thick filaments. This arrangement allows the myosin heads, which protrude all around the thick filament, to attach to the actin filaments

38. Transverse Tubule
in human skeletal muscle, each sarcomere has two transverse tubules running perpendicular to fiber
T-tubules extend through fiber and have openings at sarcolemma allowing communication with plasma
cardiac fibers have only one T-tubule which lies at Z-line

39. Sarcoplasmic Reticulum (SR)
made up of terminal cisternae and longitudinal tubules
serves as a storage depot for Ca2+
terminal cisternae abut T-tubules
longitudinal tubules cover myofibrils and connect terminal cisternae

40. 1. On what component does Ca2+ bind to?
Sarcoplasmic reticulum
Myosin heads
Troponin
Tropomyosin
2. What protein returns Ca2+ to the sarcoplasmic reticulum?
Myosin head
Ca2+ pump
Ca2+ channels
tropomyosin

41. Review questions
Describe the myosin filament of a skeletal muscle fiber.  Include a detailed description and function of the myosin head.
Describe the thin filament of a skeletal muscle fiber.
Describe the cytoskeleton proteins and their functions in the sarcomere.
Describe the sarcoplasmic reticulum and its role in excitation-contraction.

42. Excitation-Contraction
How muscle contracts

43. Excitation-Contraction Coupling
action potentials, generated at neuromuscular junction travel around sarcolemma and through T-tubules
T-tubules signal SR to release Ca2+ into sarcoplasm (cytosol)
Ca2+ saturates troponin (in non-fatigued state)
troponin undergoes conformational change that lifts tropomyosin away from actin filament

44. E-C Coupling (cont.)
myosin head attaches to active site on actin filament
after attaching to actin, myosin head moves actin-myosin complex forward and releases ADP and Pi
ATP binds with myosin head, which releases actin, and returns to original position
in resting state, myosin head contains partially hydrolyzed ATP (ADP and Pi)

45. Notice the “power stroke” of the myosin heads in the lower figure
Notice the “power stroke” of the myosin heads in the lower figure. It is with this step that brings about a shortening of the sarcomere.

46. E-C Coupling Schematic
In the transition of A to B, ATP must bind to the myosin head in order for it to release from the actin molecule. While bound to the myosin head, ATP is hydrolyzed (C), and upon release of the Pi (D), the myosin head undergoes a “power stroke” causing the sarcomere to shorten. ADP (E) is released in a subsequent step during which the myosin head remains attached to the actin. Only in the presence of ATP can the myosin head detach.

47. E-C Coupling (cont.)
entire cycle takes ~50 ms although myosin heads are attached for ~2 ms
a single cross-bridge produces 3-4 pN and shortens 10 nm
as long as action potentials continue, Ca2+ will continue to be released
when action potentials cease, SR Ca2+ pumps return Ca2+ ceasing contractions
skeletal motor units follow “all or nothing” principle

48. Excitation-Contraction
AP causes vesicles to release Ach
Muscle AP travels down t-tubules
SR releases Ca2+ into sarcoplasm
Ca2+ binds to troponin
Myosin heads bind to actin; mysoin ATPase splits ATP
ATP binds to myosin heat; releases from actin
Crossbridge action continues while Ca2+ is present
When AP stops, Ca2+ pumped back to SR
Tropomyosin covers active sites

49. EC Coupling QuickTime Movie of sliding filaments
Click on Link
Click on Actin Myosin Crossbridge 3D Animation
To view a great cartoon of E-C, located on the SDSU Biology 590 Human Physiology course web site, click on the link above (requires Quicktime plug-in).

50. 3. What will happen if ATP is depleted in muscle?
Nothing
Muscle will relax
Muscle will not relax
4. What will happen if sarcoplasmic reticulum of fiber is enhanced?
Fiber will develop tension more quickly
Fiber will relax more quickly
Both a and b will occur

51. Review questions
Discuss the signaling process of the T-tubules that leads to Ca2+ release by the sarcoplasmic reticulum. 
Describe ATP hydrolysis by the myosin filament. 
Discuss factors that could affect the rate of ATP hydrolysis by the myosin head as well as factors that affect tension development.

52. Skeletal Muscle Fiber Types
generally categorized by histochemical criteria
innervating nerve is primary determinant of fiber type
motor units composed of homogenous fibers
all human muscles contain mixture of three general fiber types
slow twitch (ST, oxidative, red, Type I)
fast twitch (FTa, fast-oxidative, white, Type IIa)
fast twitch (FTb, glycolytic, white, Type IIx [often called IIb])

53. stained for myosin ATPase (pH = 10.3) (dark stained)
stained for myosin ATPase (pH = 4.3) (light stained)
stained for SDH
(dark stained)
Type I
Type IIa
Type IIx

54. Muscle Twitch Characteristics
frontalis/orbicularis oculi (15% ST)
first dorsal interosseous (57% ST)
soleus (80% ST)
extensor digitorum brevis (60% ST)

55. Fiber Type Characteristics
Performance characteristics affected by:
size of motoneuron
size of muscle fibers
amount of SR
Ca2+-ATPase
myosin ATPase
aerobic capacity (amount of mitochondria)
anaerobic capacity (amount of glycolytic enzymes)
Be able to contrast the physiological characteristics of the three fiber types. Also, be able to explain how each of the bulleted items affects performance characteristics.

56. Be able to explain the differences in the force responses between motor units.

57. Fiber Type Performance Characteristics
Compare fiber types responses for the following AND provide a reason for your response:
(absolute & relative) force output
time-to-peak tension
relaxation time
shortening velocity
fatigability

58. 5. Which fiber reaches peak tension most quickly?
Type I
Type IIa
Type IIx
6. What is the reasoning for your response to Q5?
faster myosin ATPase
more Ca2+ channels
more Ca2+ pumps
faster action potentials
none of the above are correct

60. Exam 1 – Thu, Feb 8 Begin preparing for exam NOW!
Use posted learning objectives as basis for studying
Read text to clarify material
Initially, study by self, then study with classmates
“Teach” each other course material; question accuracy/completeness of other’s explanations
See me if questions remain
You may start the exam at 7:45 am
Bring the medium-sized RED scoring sheet (sheet that enables you to bubble in your name)

61. Motor Unit Recruitment Pattern – Size Principle
Note that at high exercise intensities, all three fibers types are recruited, although at low intensities, only ST fibers are recruited.

62. Quiz 1 c b e No ATP available for myosin head to detach from actin. d
ST fibers have less SR, thus Ca2+ release and uptake are slower. c a e
Force was decreasing.
Decreasing EMG represents decreasing motor unit recruitment.

63. Muscle Movements isotonic – develops tension while changing length
isokinetic – resistance to muscle changes with muscle length to ensure equal tension development
isometric (static) – develops tension but no length change
concentric – develops tension while shortening
eccentric – develops tension while lengthening

64. Muscle Performance Characteristics
Force and power development dependent on:
number of muscle fibers recruited
muscle architecture
angle of pull
length of fiber
velocity of shortening
load place on muscle

65. Length-Tension Relationship

66. Length-Tension Relationship
Be able to provide an explanation for the differences in force output of a fiber when isometrically contracted at various lengths.

67. How sarcomere length affects force output This explains the length-tension relationship

68. At which length would force output by the biceps muscle be greatest?
When the arm is in full extension
When the arm is flexed at º
When the arm is at full flexion
Strength (force) would be the same throughout the entire range of motion

69. Force-Velocity Relationship
Be able to explain and contrast the force-velocity relationships for eccentric and concentric muscle actions.

70. How would the EMG activity to a leg squat during the lowering (eccentric) phase compare to the upward (concentric) phase.
EMG activity would be the same for both phases.
EMG activity would be greater for the concentric phase.
EMG activity would be greater for the eccentric phase.

71. EMG comparison of concentric and eccentric actions
Bicep EMG activity of six arm curls. Be able to interpret the EMG activities so as to describe the changes in weight of the dumbbells. Also, note the differences in EMG activity between the concentric and eccentric phases.

72. Muscle Spindles (sensitive to stretch)

73. Golgi tendon organs (sensitive to strain)

74. Resistance Training Adaptations
dependent on neural and physiological adaptations
training specificity determines adaptations

75. Strength Training Adaptations

76. Neural Adaptations increased motor unit recruitment
decreased neural inhibition of motor unit recruitment
decreased antagonist muscle recruitment
increased neural coordination

77. Muscle Fiber Adaptations
increased fiber size (both types)
increased hypertrophy (1º)
increased hyperplasia (2º)
occurs more to FT fibers than ST
little or no change of fiber types
testosterone explains only part of larger muscle mass in males

78. an untrained individual increase strength?
How does
an untrained individual increase strength?
a trained individual further increase strength?
neuromuscular adaptations
hypertrophy
both neuromuscular adaptations and hypertrophy

79. Exercise-Induced Muscle Damage and Soreness
Unaccustomed exercise stimulates sequence of events that:
diminishes performance
causes ultrastructure damage
initiates inflammatory reaction
causes delayed-onset muscular soreness (DOMS)

80. Muscle Damage/Repair Overview
damage occurs during lengthening (eccentric) movements
damage commonly occurs to sarcolemma, Z-disk (streaming), T-tubules/SR, myofibrils, cytoskeleton
initial muscle damage followed by inflammatory-induced damage
produces muscle swelling
affects FT fibers more than ST fibers
repair begins ~3 d post-exercise

81. Z-line streaming
Note the prevalence of Z-line streaming in Figure b.

82. Muscle Fiber Damage – Sarcolemma damage
Note the prevalence of sarcolemma damage.

83. Exercise-Induced Muscle Damage
extent of injury more related to length than force or velocity
weaker fibers become overstretched, which become damaged (Morgan, 1990)

84. Popping-Sarcomere Hypotheses
Elastic filaments only linking thick filaments
Total tension is 80% of maximal tension; sarcomere is on descending limb of length-tension relation.
Popping-Sarcomere Hypotheses
Additional elastic element
When half of sarcomere is over-stretched, tension is increased on additional elastic element, which increases passive tension.
Top number reflects % of tension developed by additional elastic element; middle number reflects isometric tension developed by cross-bridges; lower number reflects tension developed by series elasticity. Top and bottom numbers reflect passive tension, thus, passive tension in whole sarcomere becomes significant when half becomes overstretched.
Proske & Morgan, J Physiol, 2001

85. Stages of Muscle Damage
1. During exercise:
Mechanical (strain) damage results in:
sarcolemma damage
SR damage
myofibrillar damage
Ca2+ influx
2. After exercise:
Inflammatory response causes:

86. Effects of Elevated intracellular Ca2+
activates proteases
damages cytoskeleton proteins
activates phospholipases
generates free radicals
damages plasma membranes

87. Acute Phase Response
Promotes clearance of damaged tissue and initiates repair
 circulating neutrophils (w/in 1-12 h) and monocytes (w/in 1-3 d)
enters injury site and phagocytizes damaged tissue
release cytotoxic factors (e.g., oxygen radicals)

88. Typical Times of Peak Effects
Ultrastructural damage  3-d postexercise
DOMS  1-2 d postexercise

89. Effects of Eccentric Arm Curls (on a scale of 0 to 6)
Kolkhorst et al., ACSM, 2003

90. Effects of Eccentric Arm Curls
Kolkhorst et al., ACSM, 2003

91. CK from 60-min Downhill Running
Kolkhorst, unpublished observations

92. Effects on Performance/Soreness
greater damage to FT fibers
prolonged strength loss
primary cause  failure of SR-Ca2+ release
ultrastructure damage secondary cause of strength loss
muscle swelling/DOMS
DOMS caused by tissue breakdown products that sensitize pain receptors

93. Muscle Repair
macrophage infiltration required for activation of satellite cells
satellite cells located between basement membrane and plasma membrane
in response to signal from injury site, satellite cells migrate to injury
differentiate into myoblasts, which fuse into myotubes

94. Muscle repair

95. Immediately after crush injury
2 days
At 2 d, damaged fibers have undergone necrosis, with digestion/removal by macrophages.
At 5 d, several newly formed myotubes are visible.
At 10 d, myotubes have transformed into fibers, many of which have linked up with fibers stumps on either side.
5 days

96. Adaptation to Eccentric Exercise
adaptation occurs w/in 1 week
 number of sarcomeres?
increases fiber length,
Allows sarcomere to work at shorter lengths

97. Quiz 2 e a d d Increased motor unit recruitment c
Measure EMG during max lift before and after training. Post-training EMG should be greater. c a d c
Maximal number of cross-bridges occur at this muscle length b
If fiber contracts, it develops its maximal tension
Yes, but fibers develop more tension during eccentric movement

98. Which type of activity would likely cause the most severe DOMS or muscle damage?
level running (involves about half concentric and half eccentric movements)
rowing exercise (involves mostly pulling motion, a concentric movement)
running down stadium stairs (involves more eccentric than concentric movements)
cycling (entirely concentric movements)
none of the above would cause DOMS

99. Eccentric exercise
causes the greatest damage at the shortest muscle lengths.
causes the greatest damage to ST fibers.
initiates an inflammatory response that causes further myofibril damage.
stimulates macrophage infiltration to the damaged area, which is essential for muscle repair.
both c and d are correct

100. The greater the load placed on a muscle during a shortening movement, the _____ it can shorten. This illustrates the _____ relationship of skeletal muscle mechanics.
slower; power-load
slower; length-tension
faster; length-tension
slower; force-velocity
faster; force-tension

101. According to the Force-Velocity relationship, how does force output of a fiber when shortening compare to when it is forced to lengthen?
force output is greater when it is allowed to shorten
force output is equal regardless of shortening or lengthening
force output is less when it is allowed to shorten