1.9A. (Neuromuscular junction) and physiology of the skeletal muscle.

Question 1

I. Physiology of skeletal muscle
1. Characteristics of skeletal muscle

Answer 1

1/ Muscle which is attached and acts on the skeleton (movement of joints).
2/ Mediates mechanical movement of the limbs and other parts of the body.
3/ Under voluntary control by CNS (some involuntary -> reflexes)

Question 2

I. Physiology of skeletal muscle
1. Characteristics of skeletal muscle

Answer 2

1/ Muscle which is attached and acts on the skeleton (movement of joints).
2/ Mediates mechanical movement of the limbs and other parts of the body.
3/ Under voluntary control by CNS (some involuntary -> reflexes)

Question 3

I. Physiology of skeletal muscle - Structure of skeletal muscle
2A. Characteristics of skeletal muscle fibers

Answer 3

Striated, cylindrical, multinucleated fibers
- Cells = muscle fibers

Question 4

I. Physiology of skeletal muscle - Structure of skeletal muscle
2B. What are the 3 layers of Connective Tissue

Answer 4

3 connective tissue (elastin, collagen) layers
1/ Epimysium wraps the whole muscle
2/ Perimysium wraps fascicles (=bundle of muscle fibers)
- Contain blood vessels + nerves
3/ Endomysium wraps each muscle fiber

Question 5

I. Physiology of skeletal muscle - Structure of skeletal muscle
2C. What are the characteristics of myofibrils? (contractile elements)

Answer 5

1/ Each muscle fibers contains myofibrils (contractive elements)
2/ myofibrils are surrounded by sarcoplasmic reticulum (ER that surrounds the myofibril, regulates [Ca2+]IC)
3/ sarcolemma (plasma membrane of muscle fiber)
4/ invaginated by transversal tubules (T-tubules)
5/ longitudinal tubules of the SR that end in the terminal cisternae
- terminal cisternae: portion of SR nearest T- tubule, site of Ca2+-release (high density of SERCA)

Question 6

I. Physiology of skeletal muscle - Structure of skeletal muscle
2D. What is the triad of sarcolemma?

Answer 6

The triad that contains
- 1 transverse tubule of the sarcolemma
- 2 terminal cisternae of the longitudinal tubule of the SR

Question 7

I. Physiology of skeletal muscle - Structure of sarcomeres
3A. What is the relationship between myofibrils and sarcomeres?

Answer 7

Myofibrils are divided into repeating units of muscle cell called sarcomeres, which make the stripes/band pattern called ‘’striation’’

Question 8

I. Physiology of skeletal muscle - Structure of sarcomeres
3B. What are sarcomeres?

Answer 8

Sarcomeres are the basic contractile unit, composed of thick and thin filaments
-> Thin filaments anchored to Z-line, while thick filament is attached to the M-line (center of the sarcomere)

Question 9

I. Physiology of skeletal muscle - Structure of sarcomeres
3C. What are the characteristics of thick filaments?

Answer 9

1/ Thick filament is attached to the M-line (center of the sarcomere)

2/ Thick filament contains…
- myosin, which has 1 pair of heavy chains, and 2 pairs of light chains -> Together they form 2 ‘’heads’’ (has ATPase activity) which bind to actin (cross- bridges = 2 heads + myosin ‘’arm’’)

Question 10

I. Physiology of skeletal muscle - Structure of sarcomeres
3D1. What are the characteristics of thin filaments?

Answer 10

1/ Thin filaments anchored to Z-line

2/ Thin filament contains 3 proteins which are actin, tropomyosin and troponin

Question 11

I. Physiology of skeletal muscle - Structure of sarcomeres
3D2. Characteristics of actin (on thin filaments)

Answer 11

It is the long base that interacts with myosin for contraction (double helix)

Question 12

I. Physiology of skeletal muscle - Structure of sarcomeres
3D3. Characteristics of Tropomyosin (on thin filaments)

Answer 12

Tropomyosin runs along the groove of twisted actin filament.
- At rest Tropomyosin blocks the myosin-binding sites on actin.
- Tropomyosin has to move for contraction to occur

Question 13

I. Physiology of skeletal muscle - Structure of sarcomeres
3D4. Characteristics of Troponin (on thin filaments)

Answer 13

It is a complex of 3 proteins

1/ Troponin T (TnT): attaches troponin complex to tropomyosin

2/ Troponin I (TnI): (for inhibition) inhibits the interaction of actin and myosin by blocking the binding site

3/ Troponin C (TnC): if [Ca2+]IC is high, then calcium binds here, causing conformational change that moves tropomyosin out of the way, so myosin can bind to actin

Question 14

II. The electrochemical coupling
1. What is the electrochemical coupling?

Answer 14

1/ Definition: It is the process by which an electrical stimulus triggers the release of Ca2+ by the SR, initiating the muscle contraction
2/ The AP is extremely short (~5ms), and the increase in [Ca2+]IC begins shortly after the depolarization and peaks, then the increased [Ca2+]IC causes a twitch contraction

Question 15

II. The electrochemical coupling
2. What is the summary of electrochemical coupling in 1 sentence?

Answer 15

The AP is extremely short (~5ms), and the increase in [Ca2+]IC begins shortly after the depolarization and peaks, then the increased [Ca2+]IC causes a twitch contraction

Question 16

II. The electrochemical coupling
3. What is the 4-step mechanism of electrochemical coupling?

Answer 16

1. AP propagates to the T-tubules of the sarcolemma
2. Membrane depolarization causes the conformational change of DHP (dihydropyridine receptor) (L-type VG Ca2+- channel)
3. Ryanodine receptors (RYR) (Ca2+-sensitive Ca2+-channel) is activated (opened) via mechanical coupling
4. Ca2+-ions are released from the SR through the RYR -> [Ca2+]IC increases -> activates troponin C -> muscle contraction

Question 17

III. How does Ca2+-ion cycle work?

Answer 17

• Na+/Ca2+-exchanger & Ca2+ pump in the plasma membrane remove Ca2+ from the cell
• SERCA (sarco-endoplasmic reticulum Ca2+-ATPase) sequesters/isolates Ca2+ within the SR
• Ca2+ is stored in the SR by binding to calreticulin, calsequestrin, histidine rich Ca2+-binding protein

Question 18

IV. Cross-bridge cycle
1. What happen before the cross-bridge formation?

Answer 18

Prior to the cross-bridge formation::
1. The ACh (released by a motor neuron) combines with receptors on muscle fiber, causing depolarization and an AP is generated

2. AP spreads through T tubule -> Ca2+-ions released from the SR
3. Ca2+-ions bind with TnC, causing a conformation change
   ->TnC facilitates movement of tropomyosin toward the cleft of actin filament = exposure of myosin binding sites on the filament

Question 19

IV. Cross-bridge cycle
2. What happen during myosin cross-bridge cycle? (6 steps)

Answer 19

During myosin cross-bridge cycle:
1. Myosin head binds to actin filament

2. Myosin undergoes the ‘’power stroke’’, which pulls the actin filament toward the center of the sarcomere
   (sliding filament theory: length of the sarcomere shortens, force is developed)
3. Myosin releases ADP and Pi before ATP binds to myosin head
4. Binding of ATP to myosin decreases the affinity of myosin for actin
   -> Myosin head detaches from the actin filament
5. Myosin partially hydrolyzes the ATP
   -> Part of the energy in the ATP is used to ‘’recock’’ the head = ready to start once again
6. If [Ca2+]IC remains elevated, myosin undergoes another cross-bridge cycle

Question 20

IV. Cross-bridge cycle
3. What happen when no ATP is bound to myosin?

Answer 20

When no ATP is bound, myosin is tightly attached to actin in ‘’rigor’’ position. If the muscle is severely lacking ATP, as in the case of recent death, this causes the stiff muscles in rigor mortis.

Question 21

IV. Cross-bridge cycle
4. What is the sliding filament theory?

Answer 21

length of the sarcomere shortens, force is developed

Question 22

V. Mechanism of muscle contraction
1A. List 3 types of muscle contraction

Answer 22

1. Isometric contraction
2. Isotonic contraction
3. Auxotonic contraction

Question 23

V. Mechanism of muscle contraction
1B. What is isometric contraction?

Answer 23

Muscle contraction without change in length of muscle, tension (tone) on the muscle increases (Ex: as in pushing against a wall)

Question 24

V. Mechanism of muscle contraction
1C. What is Isotonic contraction?

Answer 24

muscle contraction without change in the force of contraction (tone), length changes (Ex: normal weightlifting)

Question 25

V. Mechanism of muscle contraction
1D. What is Auxotonic contraction?

Answer 25

both length and load varies during contraction (mixture of isometric and isotonic contraction)

Question 26

V. Mechanism of muscle contraction
2A. What is the length-tension relationship?

Answer 26

1. Refers to the amount of tension that can be developed from various lengths of a muscle.
2. There is an optimal length a muscle should be for the maximal amount of tension it can generate, but the muscle is weaker if it is either longer or shorter than this length
   - If muscle is too short, thick and thin filament are mushed together and cannot function
   - If the muscle is too long, thick and thin filaments are too far apart to interact
3. The voluntary movement of the muscle creates active tension, but there is also some passive tension that arises when the muscle is stretched too long from the elasticity of the muscle
   -> Active + passive tension = total tension
   => When the muscle is stretched to longer lengths, # of possible cross bridges is reduced and active
   tension is reduced. Also, when muscle length is decreased, the thin filaments collide with each other in the center of the sarcomere, thus reducing # of possible cross-bridge. So optimal is between them.

Question 27

V. Mechanism of muscle contraction
2B. Characteristics of Passive tension

Answer 27

Passive tension occurs by simply stretching a muscle to different length.

Question 28

V. Mechanism of muscle contraction
2C. Characteristics of Total tension

Answer 28

Total tension is tension developed when a muscle is stimulated to contract at different preloads/ muscle length = tension developed by cross-bridge cycling + passive tension by stretching muscle.

Question 29

V. Mechanism of muscle contraction
2D. Characteristics of Active tension

Answer 29

Active tension (total tension – passive tension) describes that the active tension developed is proportional to the number of cross-bridges.

Question 30

V. Mechanism of muscle contraction
3. What is Effect of afterload on muscle contraction: force-velocity relationship?

Answer 30

• Force-velocity relationship describes the velocity of shortening when the force against which the muscle contracts (afterload) changes. Fixed force = isotonic contraction.
• Velocity of shortening corresponds to the speed of cross-bridge cycling.
• As the afterload or force increases, velocity of shortening decreases.

Question 31

VI. Modulation of contraction force
1. What is the relationship between AP and contraction force?

Answer 31

• 1AP=1twitch
• There is no contraction without motor neuron AP
• The force of contraction is determined by AP frequency -> increasing frequency will
  move the contractions closer, so they begin to overlap and eventually will be summated

Question 32

VI. Modulation of contraction force - Temporal summation
2A. What are Electric, chemical and mechanical events in striated muscle?

Answer 32

• Ca++-outflow and muscle twitch: after AP
• Refracter period is over
  *Muscle can be stimulated again
• Contraction summation
• tetany
  -> Skeletal muscle can be tetanized

Question 33

VI. Modulation of contraction force - Temporal summation
2B. Characteristics of a twitch

Answer 33

• A single AP releases Ca2+ in amount only sufficient to cause a twitch
• Duration of contraction is short, because Ca2+ is quickly pumped back into the SR

Question 34

VI. Modulation of contraction force - Temporal summation
2C. Characteristics of a SUMMATION

Answer 34

• If the muscle is stimulated again before it is fully relaxed, the force of contraction increases
  -> Twitch forces are amplified as stimulus frequency increases
• At the intermediate stimulus frequency, [Ca2+]IC returns to baseline just before next stimulus, however there is a gradual rise in force (incomplete tetanus)

Question 35

VI. Modulation of contraction force - Temporal summation
2C. Characteristics of a Tetanus

Answer 35

• At a high AP frequency, twitch forces are amplified and [Ca2+]IC increases and maintained throughout the period of stimulation (tetanus force)

Question 36

VI. Modulation of contraction force - Temporal summation
3. How is muscle force recruited?

Answer 36

• Increased force of contraction of a muscle = increases number of muscle fibers contracting
• A muscle recruits more muscle fibers by recruiting more motor units, as all the muscle fibers within a motor unit are already activated simultaneously

Question 37

VII. Types of skeletal muscle fibers
1. List 3 types of muscle fibers

Answer 37

1. Slow-oxidative fibers (type I)
2. Fast-oxidative-glycolytic fibers (type IIa)
3. Fast-glycolytic fibers (type IIb)

Question 38

VII. Types of skeletal muscle fibers
2. Characteristics of Slow-oxidative fibers (type I)

Answer 38

• It combine low myosin- activity with high oxidative capacity.
• Red fibers, myoglobin and mitochondria
• Antigravitational, slow, fatigue-resistant

Question 39

VII. Types of skeletal muscle fibers
3. Characteristics of Fast-oxidative-glycolytic fibers (type IIa)

Answer 39

• Fast-oxidative-glycolytic fibers (type IIa) combine high myosin-ATPase activity with high oxidative capacity and intermediate glycolytic capacity.
• Red, fatigue-resistant, fast

Question 40

VII. Types of skeletal muscle fibers
4. Characteristics of Fast-glycolytic fibers (type IIb)

Answer 40

-combine high myosin- ATPase activity with high glycolytic capacity.
- White, fast, fatiguable (glycolytic=lactate!)

Question 41

VII. Types of skeletal muscle fibers
5. Make a comparison between muscle fibers

Answer 41

Question 42

VIII. Muscle fatigue
1. What is muscle fatigue?

Answer 42

Muscle fatigue is a symptom that decreases your muscles’ ability to perform over time.

Question 43

VIII. Muscle fatigue
2. What are characteristics of muscle fatigue?

Answer 43

1. Metabolic byproducts are important factors in the onset of fatigue.
2. Fatigue is not from ATP depletion, but may be from
   - Neurotransmitter (acetyl- choline) depletion
   - metabolite accumulation
   - Lack of O2-and nutrients

Question 44

VIII. Muscle fatigue
3. What happen if there is an accumulation of lactate in myoplasm?

Answer 44

1. myoplasmic pH ↓
2. Accumulation of lactate
3. Myoplasmic pH ↓
4. Ca2+-binding to troponin ↓

Question 45

VIII. Muscle fatigue
4. What happen if there is an accumulation of Pi in working muscle?

Answer 45

• Ca2+-release from SR↓
• Ca2+-sensitivity ↓
• Alteration of actin-myosin binding

Question 46

VIII. Muscle fatigue
5. Can you name other factors that can cause muscle fatigue?

Answer 46

• K+↑
• O2↓
• Nutrients (glycogen)↓
• Oxygen derived free radicals ↑
• ACh stores ↓
• Pain