MSS: Muscle Structure and Adaptation

Question 1

What is muscle formed from?

Answer 1

somites (paired blocks of paraxial mesoderm on either side of the notochord)

Question 2

Somitogenesis

Answer 2

formation of somites

Question 3

How do somites form?

Answer 3

by paracrine signalling from the neural tube and notochord triggering a mesenchymal-to-epithelial transition of the paraxial mesoderm, forming a hollow ball of epithelial cells (epithelial somite)

Question 4

What happens to the epithelial somite?

Answer 4

due to other paracrine signalling, epithelial somite further subdivided into 4 major cells which go on to form specific tissue types:

• sclerotome
• myotome
• syndetome
• dermomyotome

Question 5

Sclerotome forms…

Answer 5

bone, ribs and cartilage

Question 6

Myotome forms…

Answer 6

muscle precursors (which form muscle)

Question 7

Syndetome forms…

Answer 7

tendons

*syndetome is in between myotome and sclerotome

Question 8

Dermomyotome forms…

Answer 8

the new source of muscle cells that later populate the myotome and give rise to the dorsal dermis

Question 9

myogenesis.

Answer 9

the process by which embryonic mesoderm cells of the myotome become muscle tissue

Question 10

Steps of myogenesis

Answer 10

1) Paracrine factors signal for the mesodermal cells to produce myogenic regulatory factors Myf5 and MyoD, which commit those cells to a myogenic fate and become myoblasts
2) Myoblasts then differentiate and proliferate in presence of growth factors until they exit the cycle after expression of another myogenic regulatory factor Myogenin
3) Myogenin causes terminal differentiation of muscle fibres and differentiates the myoblasts into myotubes, and structural proteins start being expressed (e.g. myosin + actin)
4) Myotubes align and fuse together to form multinucleated muscle fibres.

Question 11

Why is muscle development biphasic?

Answer 11

After the initial formation of large primary muscle fibres, smaller secondary muscle fibres then form on their surfaces which make up the bulk of the muscle

Question 12

Satellite cells

Answer 12

third group of muscle cells (primary and secondary fibres, satellite cells)

• they are undifferentiated muscle precursors and are self-renewing.
• muscle stem cells which sit dormant on muscle fibres until they are activated in the case of regeneration and postnatal growth where they can start dividing and forming myotubes which then fuse to form the muscle fibres

Question 13

Embryonic muscle fibre number

Answer 13

at the end of embryogenesis, the number of muscle fibres that you have are what you have for the rest of your life (muscle fibre number is therefore set from birth and this is genetically determined)

-HOWEVER can be manipulated during embryogenesis

Question 14

What affects fibre number during embryogenesis?

Answer 14

Our muscle fibre number is set at determined; thus, it is genetically determined.

However, the fibre number can be affected by:

• temperature
• hormones
• nutrition
• innervation

These affect myogenic regulatory factor (MRF) expression e.g. My5, MyoD and Myogenin

Question 15

Fibre number is increased by…

Fibres increase in mass by…

Answer 15

hyperplasia

hypertrophy (increasing muscle mass postnatally)

Question 16

Postnatal Hypertrophy (increase in skeletal muscle mass)

Answer 16

After birth, an increase in muscle mass is due to an increase in fibre size (hypertrophy).

muscle fibres require more protein and therefore muscle stem cells (satellite cells) start dividing and making myotubes which fuse to make muscle fibres, producing more structural proteins
-increases cross-section and size of the muscle fibre
They maintain the cytoplasm: nuclei ratio in the muscle fibre.

Question 17

Why are muscle fibres multinucleated?

Answer 17

This is done to supply the increased production of structural proteins for the proper functioning of the muscle fibre.

Also, the muscle fibres require a lot of mitochondria, and a lot of the genes needed for mitochondria production is found in the nuclei.

Question 18

Variability between muscles

Answer 18

all sarcomere structure is the same, however, there is a lot of molecular variability between muscles due to multiple isoforms of myofibrillar proteins produced by alternative splicing or promoters

Question 19

Give some examples of myofibrillar protein isoforms, and what differs between them.

Answer 19

MYOSIN isoforms:

• different chemo-mechanical transduction
• ATP hydrolysis
• more rapid/speed of contraction

TROPONIN and TROPOMYOSIN isoforms:
- sensitivity to Ca2+

TITIN isoforms:
- elastic properties

Question 20

Which isoforms contribute to resistance to fatigue?

Answer 20

Myosin and Troponin isoforms

Question 21

Types of Muscle Fibre

Answer 21

Type I Muscle Fibres (slow twitch)

Type II Muscle Fibre (fast twitch)

Question 22

List the differences between Type I and Type II muscle fibres.

Answer 22

TYPE I:

• -produce slow maintained contraction which doesn’t easily fatigue (virtually inexhaustible)
• high mitochondria (aerobic metabolism and oxidative phosphorylation)
• more predominant in long-distance runners
• extensive blood supply and abundant myoglobin (Red muscle)
• Gastrocnemius (calf muscle) & Soleus (calf)

TYPE II:

• fatigue easily
• -fewer mitochondria and undergo mainly anaerobic respiration in a glycolytic nature (anaerobic metabolism)
• more predominant in sprinters
• poor vascularisation and lack of myoglobin (‘white muscle’)
• found in Lateral rectus (eye muscle) and Gastrocnemius (calf muscle)

Question 23

Myosin Gene Cluster

Answer 23

there are 11 myosin heavy chain genes clustered on chromosome 17 which allow for the different isoforms which give the different properties to the muscle fibres.

main types of myosin in adults:

• Fast IIX fibres
• Fast IIA fibres
• Fast IIB fibres
• Slow muscle (Type-I/β) and heart

Question 24

List some effects of training specific muscle fibre types.

Answer 24

Untrained individuals have a 1:1 ratio of fast (IIA and IIX) to slow (I) twitch fibres.

• long and middle distant runner have about 60-70% slow twitch
• sprinters have about 80% fast twitch
• trainees for sports that require the greatest aerobic and endurance capacities have slow muscle up to 90-95%
• trainees for sports that require greater anaerobic capacities (strength and power) have fast muscle around 60-80%

Question 25

How would a marathon runner’s muscles be adapted to their sport?

Answer 25

1. Muscles are small but fatigue-resistant
2. Muscles are dense and strong for their size, with a high oxidative capacity of the muscles
3. They can work over very long periods of time
4. They don’t contain explosive strength

Question 26

How would a sprinter’s muscles be adapted to their sport?

Answer 26

1. Muscles produce rapid, powerful contractions
2. Muscles are easily fatigued at maximum effort
3. Muscles have a low oxidative capacity via mitochondria
4. Muscle can exert a high force per cross-sectional area of muscle

Question 27

How would a power lifter’s muscles be adapted to their sport?

Answer 27

1. Muscles are hypertrophied
2. They are highly glycolytic
3. They fatigue easily
4. Have a high muscle to total body mass ratio
5. Muscle size begins to interfere with locomotion

Thus, the power lifter is moving along the same path of adaptation as the sprinter, but more extreme.
Their power to weight ratio is moving to a point where they are less able to move their body through a distance, and hence would be less fast at running.

Question 28

Describe the gender differences in skeletal muscle.

Answer 28

There are over 3000 genes that are different between male and female skeletal muscle.

TYPE I:
M - 36%, female - 44%

TYPE IIA:
M - 41%, F - 34%

females: more slow-twitch fibres
males: more fast-twitch fibres

males have a larger fibre cross-sectional area as male skeleton is more easily hypertrophied than women (mainly due to testosterone)

Question 29

Adverse effects of synthetic anabolic steroids

Answer 29

High blood pressure

Cardiac and Respiratory Problems

Liver Disease

Question 30

Muscle Regeneration

Answer 30

DEGENERATION/INFLAMMATORY PHASE (first few days)

• myofibre rupture and necrosis
• formation of haematoma in the injured area
• inflammatory response where neutrophils start removing debris

REGENERATION PHASE (4/5 days post-injury)

• satellite cells activated and proliferate, and increased expression of myogenic regulatory factors Myf5, MyoD and Myogenin
• myotubes formed, formation of structural proteins and sarcomeres
• phagocytosis of damaged tissue

REMODELLING PHASE

• maturation of regenerated myofibres
• restoration of blood supply and innervation
• recovery of muscle function capacity
• if damage too severe, there is fibrosis and scar tissue formation

Question 31

Describe testosterone, and how it contributes to muscles.

Answer 31

Testosterone is a natural anabolic-androgenic-steroid (AAS).
promotes muscle differentiation at the expense of fat cells
-commits mesenchymal pluripotent cells into the myogenic lineage and inhibits adipogenesis through an androgen receptor-mediated pathway
-this stimulates the proliferation of satellite cells, increases structural muscle protein synthesis and causes fibre hypertrophy

Question 32

How does muscle repair differ with the type of injury?

Answer 32

In the case of a minor injury, we get the recruitment of satellite cells to the muscle fibre. The damaged muscle fibre necroses, and there is an inflammatory response. Macrophages and neutrophils will respond to the inflammation. There is an increase in satellite cell proliferation, which fuse with the muscle fibre and regenerate it.
Thus, this injury is reversible.

In the case of more severe injury, there is incomplete regeneration of muscle fibre, and so fibrotic tissue forms.

Question 33

How does testosterone help in treating muscle disease?

Answer 33

It can help elderly patients who have lost muscle mass due to age.
It can also be used to alleviate muscle loss in muscle-wasting diseases.

Question 34

Describe sarcopenia.

Answer 34

Sarcopenia is the age-related loss of muscle mass. There is a 3-8% decrease per decade after the age of 30, and gets higher after the age of 60.

It has an impact on the elderly; they are more prone to injury and disability from falls, etc.
It’s associated with decreased satellite cells number and recruitment.

There are biochemical and metabolic changes:

• mitochondrial mutations
• reduced oxidative and glycolytic enzyme activity
• reduced endocrine functions
• reduced physical activity