S3: Muscle Structure and Adaptations: The Genetic Plan and How it can change our lives

Question 1

Describe Myogenesis

Answer 1

• There is initially uncommitted mesodermal cells.
• Paracrine factors induce Myf5 and MyoD causing myogenic commitment of mesodermal cells into myoblasts. Another signal causes cell cycle to end and this is regulated by myogenin which causes terminal differentiation.
• Structural proteins are expressed and myotubes form. The myotubes align and fuse to make one big cell (muscle fibre). The muscle fibres are multinucleated.

Question 2

How does muscle develop biphasic pattern?

Answer 2

• Initially primary muscle differentiates into myotubes which forms the structure for another phase of myogenesis where a secondary pool of muscle then adds to the infrastructure.
• There is a third pool of myoblasts that don’t differentiate called the satellite cells (the muscle stem cells) that lie dormant until activated. The satellite cells are used for regeneration and post natal growth.

Question 3

What determines muscle fibre number?

Answer 3

Muscle fibre number is set at birth and genetically determined. However, fibre number can be affected by various factors we are born with:
- Temperature
- Hormones
- Nutrition
- Innervation
These also affect MRF (myogenic regulatory factors)expression duration.

Question 4

How do muscle mass grow?

Answer 4

Muscle mass grows by a process of hypertrophy by increasing the muscle fibre size but not the number of fibres.

Question 5

What are Muscle stem cells (MuSCs)?

Answer 5

Muscle stem cells (MuSCs) are called satellite cells. They are undifferentiated muscle precursors that are self renewing. MuSCs have little cytoplasm and are mostly nucleus.

Question 6

Describe postnatal muscle growth by hypertrophy

Answer 6

After birth, increase in muscle mass due to increase in fibre size (hypertrophy). MuSCs proliferate and are incorporated into muscle fibres. They are able to generate more protein in the muscle fibre (increased protein synthesis) and muscle mass increases. They return to quiescence when not needed.

Question 7

Why do muscle fibres maintain a nuclei:cytoplasm ratio (they are multinucleated)?

Answer 7

To maintain a high rate of protein synthesis.

Question 8

Describe layers of muscle structure

Answer 8

• 100-1000 myofibrils form a muscle fibre.
• Muscle fibres in bundles form Fasiculi.
• Muscle fibre (one cell) membrane is called the sarcolemma.
• Sarcoplasm contains glycogen, fat, enzymes and mitochondria.
• Sarcoplasmic reticulum is involved in Ca2+ release.

Question 9

What is a sarcomere?

Answer 9

It is a contractile unit (smallest contractile unit of muscle) and is made up of thick and thin filaments.

Question 10

Describe sarcomere

Answer 10

• Anisotropic band: high density (thick) filaments.
• Isotropic band: actin filaments.
• Titin, giant molecular spring which connects the myosin to the z line is found at the end of each band.
• M line in the middle is where the myosin is bound together.

Question 11

What does the sliding filament model (1950) show?

Answer 11

• A band stayed the same during a contraction but the I band shrunk (distance between z lines).
• Actin filaments slide in between thick myosin filaments.
• Requires ATP to facilitate the sliding action.

Question 12

What happens when motor neurone stimulates Ca2+ release at sarcomere?

Answer 12

• Ca2+ binds to troponin, tropomyosin conformational change and myosin binding sites become unblocked.
• Myosin head attach to binding site
• Power and stroke movement along the actin
• New ATP causes myosin bridges to detach
• ATP re-cocks the myosin head ready for the next cycle-

Question 13

How is there muscle fibre type diversification?

Answer 13

All vertebrae sarcomere structure is the same across multiple species. However, there is huge molecular variability depending on function across species and muscle types due to alternative splicing or promoters during protein synthesis (forms multiple isoforms of myofibrillary proteins).
- Myosin isoforms have different chemomechanical transduction, ATP hydrolysis and shortening velocity.
- Troponin and Tropomyosin isoforms determine sensitivity to Ca2+.
These two are resistant to fatigue.
- Titin isoforms determine elastic properties.

Question 14

What are the 2 main types of muscle fibres?

Answer 14

• Slow muscle (type I)

- Fast muscle (type II)

Question 15

Describe type I fibres and give example

Answer 15

e. g. back extensor muscle
- Virtually inexhaustible
- Oxidative phosphorylation
- High mitochondria so aerobic
- Extensive blood supply and abundant myoglobin

Question 16

Describe type II fibres

Answer 16

• Fatigues easily
• Glycolytic (high contractile force but fatigues easily)
• Few mitochondria: mainly anaerobic metabolism
• Poor vascularisation and lack myoglobin

Question 17

Give examples on how affects of training on fibre type

Answer 17

Untrained individuals 50:50 ratio of fast (IIA and IIX) to slow (I) twitch fibres.

• Long and middle distant runner: 60-70% slow
• Spinters: 80% fast twitch
• Sports requiring greatest aerobic and endurance capacities: slow muscle up to 90-95%
• Sport with greater anaerobic capacities (strength and power) have fast muscle from 60-80%

Question 18

How has a mathathon runners muscles adapted to the enviroment?

Answer 18

1. Muscles small but fatigue resistant
2. Muscle dense and strong for their size and have high oxidative capacity
3. Work over very long periods of time
4. Not explosive strength

Question 19

How has a sprinter muscles adapted to the enviroment?

Answer 19

Muscles adapted for explosive release of force.

1. Rapid powerful contractions
2. Easily fatigued at maximum effort (glycolytic pathway forms lactic acid which needs to be broken down)
3. Low oxidative capacity via mitochondria (slow process to gain ATP)
4. High force per cross sectional area of muscle

Question 20

How has a powerlifter muscles adapted to the enviroment?

Answer 20

Muscle adapted for immense strength:
1. Muscles are hypertrophied
2. Highly glycolytic
3. Fatique easily
4. High muscle to total body mass ratio
5. Muscle size beginning to interfere with locomotion
Thus the powerlifter is moving along the same path of adaptation as the sprinter but is more extreme.
His power to weight ratio is moving to a point where he is less able to move his body through a distance and hence would be less fast at running.

Question 21

What chromosome is the myosin gene found?

Answer 21

The myosin gene regulating slow or fast muscle fate cluster together on the chromosome (17).

Question 22

Gender differences in myosin isoforms

Answer 22

• Males have more muscle mass than female
• Females have more slow muscle than male
• Male have large cross sectional area than female (higher hypertrophied muscle)
• > 3000 genes different between male and female skeletal muscle.

Question 23

Describe testosterone

Answer 23

It is the primary male sex hormone: required for the development of the male reproductive system.
It promotes secondary sexual characteristics: muscle + bone mass, body hair, deep voice.
Testosterone is a natural anabolic androgenic steroid (AAD) promotes the commitment of mesenchymal pluripotent cells into myogenic lineage (promotes muscle leanness and gain) and inhibit adipogenesis (androgen receptor mediated pathway).
It stimulates: satellite cell replication, muscle protein synthesis, fibre hypertrophy

Question 24

What is injection of synthetic testosterone used for?

Answer 24

• Cheating in athletic sports

- It has been used to reduce osteoporosis and increase muscle mass in the elderly.

Question 25

Describe mechanism of muscle repair and regeneration

Answer 25

Muscle fibre have good ability to regenerate, but as a whole our ability to regenerate tissue compared to other species is low. If you sprain you muscle, there is initial myofibril necrosis and there is an inflammation response where macrophage come in a clear out the muscle fibre,. Then there is a regenerate response when satellite cells are activate and proliferate. They then fuse with remaining muscle fibres and start to regenerate the loss of the muscle fibre. Remodelling can then occur.
However, fibrotic tissue is often formed (scarring).

Question 26

What is DMD?

Answer 26

DMD most common severe form of childhood muscular dystrophy (1:5000 males). This is caused by a mutated gene: Dystrophin which connects sarcomere to the sarcolemma to extracellular matrix. A problem with this causes muscle wasting.
They are unable to walk by 10-12 years and death by early to mid 20s (heart failure).

Question 27

How are satellite cells affected in DMD?

Answer 27

Patients have impaired regenerative capacities however Dystrophin is not expressed in satellite cells. Interestingly, patients have elevated satellite cell numbers. Therefore not exhausted satellite cells.
Actually there is an inability for DMD satellite cells to enter the myogenic program.

Question 28

What is sarcopenia?

Answer 28

Age related loss of muscle mass.

Question 29

Describe muscle aging

Answer 29

• 3-8% decrease per decade after the age of 30, higher after 60
• ‘use it or lose it’ - push for elderly to use their muscles
• Impact on the elderly: falls, injury, disability
• Loss of muscle mass associated with gain in fat mass
• Associated with decreased satellite cell number and recruitment
• There is Biochemical and metabolic changes with age: mitochondrial mutations, reduced oxidative and glycolytic enzyme activity
• Reduced endocrine function, reduced physical activity