5. Skeletal Muscle Flashcards
1
Q
Structure of skeletal muscle
A
Striated, voluntary, many nuclei
2
Q
Major functions of skeletal muscle
A
Exert force and produce heat
3
Q
Structure of smooth muscle
A
No striations, involuntary, single nuclear. Located in the walls of hollow organs.
4
Q
Functions of smooth muscle
A
Peristalsis and control of blood flow
5
Q
Structure of cardiac muscle
A
Striated, spontaneously active, involuntary, single nucleus
6
Q
Function of cardiac muscle
A
Pumping blood
7
Q
Intercalated discs
A
A feature of cardiac muscle that holds the cells together and allows them to act as one unit
8
Q
Origin and insertion of skeletal muscle
A
Point of attachment to skeleton closest to spine is origin and point of distal attachment is insertion.
Origin and insertion occur through tendons.
9
Q
Extensor and flexor
A
Muscles that act in opposition
10
Q
5 levels of skeletal muscle organization
A
- skeletal muscle
- fasciculus
- muscle fiber
- myofibril
- myofilaments
11
Q
Sacromere
A
Basic contractile unit in skeletal muscle
12
Q
Fasciculus
A
Compartments full of muscle fibers
13
Q
Bands of sacromere
A
1/2 light, 1/2 dark
14
Q
Size of skeletal muscle fibers
A
A few millimeters to several centimeters long, but 50-60um diameter
15
Q
Function of myofilaments
A
Intracellular contractile proteins that generate force.
16
Q
Appearance of myofilaments
A
Arranged longitudinally to sacromeres. Striated appearance is a result of serial and parallel repitition of myofilaments and the differing abilities of actin and myosin containing areas to transmit light.
17
Q
A band
A
Anisotropic band. Dark, myosin. Thick filament. Centre of the sacromere.
18
Q
I band
A
Isotropic band. Light, actin. Thin filament. Anchored to Z lines.
19
Q
Components of thin filaments
A
Two chains of globular actin molecules (G-actin) twisted into two strands to form filamentous actin (F-actin).
Troponin complex and tropomyosin.
20
Q
Three globular proteins that make up troponin
A
- Troponin T (TnT): attaches the troponin complex to tropomyosin.
- Troponin I (TnI): inhibits actin and myosin interaction.
- Troponin C (TnC): binding of 4 molecules of Ca2+ to troponin C removes inhibition and permits actin and myosin interaction.
21
Q
What allows the actin filament to move
A
Binding and unbinding of tropi=onin complex
22
Q
How many actin monomers does tropomyosin span
A
7
23
Q
Components of thick myosin filaments
A
A protein with a high molecular weight (~480kDa)
One pair of heavy chains that form long rodlike segment with globular heads. Two pairs of light chains associated with the heads.
A tail region and a cross-bridge region.
The light chains are important in myosin ATPase activity.
24
Q
How many neurons supply each muscle fiber
A
One motor neuron
25
How many muscle fibers does a motor neuron innervate
Many
26
What is a motor unit
Consists of a single motor neurons and the muscle fibers that it innervates. A given muscle may include several motor units.
27
Neuromuscular junction
The chemical synapse between a motor neuron and skeletal muscle cell
28
Steps in neuromuscular transmission
1. Neuronal action potential enters axon terminal
2. Membrane depolarizers (cell becomes more positive to reach threshold due to influx of sodium in axon terminal
3. Calcium dependent channel opens.
4. Calcium binds to proteins which causes neurotransmitter vesicles to fuse (aka vesicular fusion)
5. ACh binds to post-junctional receptors (nicotinic receptors)
6. nAChR allows sodium and potassium to pass through the opening channels
7. Depolarization of motor end plate (EPP) occurs because sodium moves in and potassium leaks out
29
Hemicholinum
Inhibits choline/Na+ reuptake. Clinical significance.
30
Botulinum toxin
Blocks NT release, leads to paralysis. Treatment for migrained, cross eyes, and wrinkles.
31
Curare
Binding to the channel receptor, prevents it from opening, no AP signal transfer. Analgesic, relaxations.
32
Neostigmine
ACh won't be broken down.
| Allow ACh to stay for a longer time, longer muscle contraction.
33
Pathophysiology of myasthenia gravis
Normally there is an excess amount of ACh receptors and a lot more ACh is released than is needed for depolarizing the muscle membrane.
Myasthenia gravis is an autoimmune disease that destroys ACh receptors.
Characterized by skeletal muscle weakness and fatigue.
The amplitude of muscle endplate potential is reduced and therefore it is more difficult to depolarize the muscle membrane to threshold for action potentials.
34
Treatment for myasthenia gravis
Acetylcholine esterase inhibitors, to prolong the action of ACh and compensate for the reduced number of receptors
35
Myofilament arrangement in a sacromere
M-line is the center
Sacromere is Z line to Z line
A band is thick filaments, I band is only thin filaments.
36
Sliding mechanism of muscle shortening
1. sacromeres shorten
2. A band length remains constant
3. I band length becomes shorter.
4. Myofilament lengths remain constant - slide past one another.
37
Dystrophin
A cytoskeletal protein that links actin filaments to the extracellular matrix via a complex of transmembrane proteins. Dystrophin defects cause muscular dystrophies.
38
Cause of Duchennes muscular dystrophy
Dystrophin defects
39
Where is dystrophin attached to the actin cytoskeleton
The N terminus
40
Titin
Largest human protein, elastic properties, associated with thick filaments. When the sacromere length changes, the length of the elastic part of the titin, anchored to the Z-disk, also changes. Titin protects muscle fibers from damage due to overstretching.
41
Nebulin
A large actin binding protein. It sets the length and orientation of thin filaments during their assembly.
42
Transverse (T) tubules
Invaginations of sacrolemma. The depolarization spreads from muscle fiber surface to its interior via T-tubules.
43
Sacroplasmic reticulum
Sacroplasmic reticulum (SR) is an internal membrane system of the muscle cell, stores Ca2_ in the terminal cisternae.
44
Excitation-contraction coupling in skeletal muscle
The process by which the excitation of a muscle cell (AP) is coupled to increase in intracellular Ca2+ concentration and the cross-bridge cycle.
AP, then [Ca2+]in increase, then muscle tension
45
Steps of excitation-contraction coupling
1. Ach released from synaptic terminal, muscle depolarization
2. AP propagates to T-tubules, activates DHPR receptors
3. Calcium is released from SR via ryanodine receptors into the muscle fiber
4. Calcium binds to troponin, tropomyosin reveals the myosin binding site on actin
5. Myosin attaches to actin, and APT hydrolysis allows sliding and contraction
6. Contraction ends when calcium is pumped by into SR via ATP driven SERCA-pump
46
Dihydropyridine receptors
Voltage-gated Ca2+ channels at the T tubules. They undergo conformational changes as the AP moves down the T tubule, leading to activation of ryanodine receptors (RYR) on the SR.
47
Ryanodine receptors
Activated by AP, lead to Ca2+ release into muscle fiber from the SR.
48
SERCA pump
At rest, Ca2+ is pumped from muscle fiber into SR. ATP driven,
49
Calcium in the SR
Bound to Ca2+ binding protein, calsequestrin. Calsequestrin holds up to 4 calcium.
50
Cross-bridge formation regulation
Ca2+ binding to troponin regulates the cross-bridge formation
51
Cross-bridge cycle
1. Rest: Troponin complex on the thin filament have no bound Ca2+ and tropomyosin is positioned so as to block the binding sites on the actin. Myosin is energized.
2. Ca2+ binds to troponin: Energized myosin binds to actin. Ca2+ binding causes a conformational change in the thin filament that exposes binding sites, allowing myosin heads to attach and form cross bridges between the thick and thin filaments. ADP remains bounded to myosin.
3. Power stroke: stored energy is released and drives thin filament movement. ADP and inorganic phosphate are released from myosin. Attached myosin heads rotate, exerting longitudinal forces that pull the thick and thin filaments into greater overlap, shortening the muscle fiber. Z line moves closer to the thick filament.
4. ATP binds to myosin: Myosin detaches from actin. Myosin then hydrolyzes ATP and undergoes a conformational change to the energized state and the cycle repeats. As long as Ca2+ and ATO are present, cycle continues and Z-lines are pulled closer to thick filaments. When there is no Ca2+, muscle relaxes to resting position.
52
What parts of the cross-bridge cycle have highest and lowest actin affinity
```
Highest = relaxed muscle (myosin bound to ADP and Pi, not actin)
Lowest = actin bound to myosin and ATP.
```
53
Roles of ATP in skeletal muscle contraction
1. Hydrolysis of ATP by myosin energizes the cross-bridges providing energy for tension generation.
2. Binding of ATP to myosin dissociates actin bound cross-bridges allowing bridges to repeat their cycle of activity.
3. Hydrolysis of ATP by SERCA pump provides energy for active transport of CA2+ ions into the sacroplasmic reticulum, lowering the cytoplasmic [Ca2+], ending contraction and allowing muscle fiber to relax.
54
Three types of skeletal muscle
Type I. Slow twitch muscle
Type II. Fast twitch muscle
Intermediate
55
Slow twitch muscle
E.g. soleus (S)
| High oxidative capacity and mitochondrial content, lots of myoglobin (red), slow fatigue, sustained activity.
56
Fast twitch muscle
E.g. lateral rectus (L.R.) in the eye.
| Glycolytic, small number of mitochrondria, small amount of myoglobin, rapid fatigue, brief activity
57
Intermediate muscle
E.g. gastocnemius (G_.
| Contains mixture of slow and fast twitch fibers and therefore intermediate tension when whole muscle is stimulated.
58
Energy sources during muscle contraction
There is only a small ATP pool in a skeletal muscle. It needs to be replenished during exercise. Can be provided through phosphagen system, glycolysis or aerobic metabolis.
59
Phosphagen system
```
Energy is stored as Creatine phosphate (CP) which is made of ATP during rest.
Can provide energy for short term, less than 1 min of muscle activity.
Creatine phosphokinase (CPK) is the enzyme that converts CP to ATP and creatine.
```
60
Glycolysis
Glycolysis does not require oxygen (anaerobic).
Net production of 2 ATP molecules
Occurs in the cell cytoplasm.
Important for quick bursts of speed or strength.
Glycolysis slows down as pyruvic acid builds up.
Pyruvic acid is converted to lactic acid which also eventually builds up, slowing metabolism and contributing to muscle fatigue.
61
Aerobic metabolism
Pyruvic acid is metabolized aerobically in the mitochondria. It is converted to an acetyl group which enters to Krebs Cycle.
Energy is released as ATP and as high energy electrons that are sent to the electron transport system which produces most ATP.
Waste products are
CO2 and H2O. The reactant (other than glucose) is O2. Aerobic metabolism is used for endurance
activities and can go on
for hours.
62
Oxygen debt
Restoration of ATP and CP levels
Metabolism of lactate
Increase in cardiac and respiratory work during recovery
63
Muscle fatigue
Metabolic by-products (e.g. lactic acid, inorganic phosphate) are important in the onset of muscle fatigue.
A series of brief tetanic stimulations results in a rapid decrease in force, which is attributable to fatigue of fast twitch (type II) motor units in the muscle. Slow twitch (type I) motor units are more resistant to fatigue.

64
Muscle fasciculation
Occurs when the motor nerve is cut (denervation): small, irregular muscle contractions caused by releae of acetylcholine.
65
Muscle fibrillation
Occurs several days after denervation: spontaneous, repetitive contractions. nACh receptors spread out over the cell membrane, muscle is now supersensitive to ACh.
66
Atrophy after denervation
Decrease in the size of muscle fibers and entire muscle. Is progressive continuing months after denervation. Most muscle fibers are replaced by fat and connective tissue after 1-2 years
67
Reinnervation
Changes from denervation can be reversed if this occurs within a few months. Normally achieved by growth of the peripheral stump of motor nerve axons along the old nerve sheath.
68
Thee categories of training regimens and reponses
1) Learning: e.g. typing. The learning aspect of training involves motivational factors, as well as neuromuscular coordination. Increased rate and accuracy of motor units (central nervous system).
2) Endurance: e.g. marathon running. Sustained training helps to increase oxidative capacity in motor units that are involved with limited cellular hypertrophy.
3) Strength training: e.g. weight lifting. Enhanced glycolytic capacity of the motor units used. Synthesis of more myofibrils and hypertrophy of the active muscle cells. Increased stress also induces the growth of tendons and bones.
Most athletic endeavors involve elements of all three.

69
Contraction
Refers to the active process of generating force within the muscle by corss-bridge activity. The force is called muscle tension and the weight or recipricol force is called load.
70
Isometric contraction
When the muscle length remains constant we measure the force (tension) generated by the contractile machinery.
Isometric contractions: maintenance of posture.
71
Isotonic contraction
Movement phases of the muscle contraction.
When the load remains constant we measure the shortening of the muscle.
Isotonic contractions: lifting the limbs.
72
The muscle twitch
Shortly after one stimulus there is an increase in muscle tension which then decays, (isometric contraction).
Latent period: no contraction (excitation-contraction coupling).
One action potential in a muscle causes a twitch, many cause a smooth
contraction.
73
Frequency-tension relationship
A temporal summation relationship.
If the muscle is stimulated second time, before it has had time to relax completely, the second response may add to the first and a greater peak tension is generated.
With increasing stimulus frequency the maximum tension is increased...
74
Tetanus
...the oscillation becomes smaller and eventually a smooth tetanic contraction is produced. The tension may be 2-3 times as great as produced in single twitch.
75
Magnitude of tetanic contraction
Normal movements are tetanic.
The magnitude of tetanic contraction is greater than that of single twitch contraction because:
1) Prolonged elevation of intracellular [Ca2+].
2) The series elastic components are fully stretched.
Tendons are series elastic components, but there are also internal components.
76
Active tension
Sliding myofilaments
Reflects the overlap of the thick and thin filaments. It is maximal when there is maximal overlap of thick and thin filaments.
77
Passive tension
Muscle is stretched without stimulation.
Produced by parallel elastic components (titin is the main component) in the muscle. This is the tension that is developed simply by stretching the muscle to different lengths without stimulation.
78
Experimental setup required to determine length-tension relation of muscle
Measures tension developed during isometric contractions when the muscle is set to fixed lengths
79
Total tension
The tension developed when a muscle is stimulated to contract at different lengths
80
Short sacromere
Actin filaments lack room to slide; little tension can be developed.
81
Optimal-length sacromere
Lots of actin-myosin overlap and plenty of room to slide
82
Long sacromere
Actin and myosin do not overlap much; little tension can be developed.
83
Force-velocity relationship
The velocity of muscle contraction is measured when the force against which the muscle contracts is varied. The muscle length can change (isotonic contraction) but the force is fixed. Maximal velocity at 0 load, decreased velocity with increased load.
