Muscle development: form and function

Question 1

What are the three categories of muscle tissue?

Answer 1

Cardiac - only in the heart
Skeletal - throughout the body involved in moving a bone relative to a bone but in the oesophagus the muscle constricts a tube (contractility of hollow organs)
Smooth - associated with the blood vessels in the gut, uterus and the bladder

Question 2

What is cardiac muscle made up of?

Answer 2

Functional syncytium of individual cardiac muscle cells called cardiomyosits

Question 3

How are cardiac muscle fibres different to skeletal muscle fibres?

Answer 3

When a longitudinal section is taken

- fibres are a series of linked single cardiac muscle cells

Question 4

How are cardiac muscle fibres structured?

Answer 4

Have an oblong structure, often in a v shape connected via the intercalated disc (mechanical and electrical function)

Question 5

What are the intercalated discs made up of?

Answer 5

1. Adherence junctions and desmosomes
   - transfer mechanical force across the heart
2. Gap junctions which are electrical connections between adjacent cardiac muscle cells
3. Arranged in contiguous sheets around the heart to give the heart its typical mechanical pumping action

Question 6

How does the heart act as syncytium?

Answer 6

Due to mechanical and electrical connections heart has a wave of depolarisation followed by a wave of contraction

Question 7

How is the desmosome structured?

Answer 7

Surrounded by actin filaments (normally a white band) and myosin filaments (normally a grey band) then another actin filament

Question 8

What is the M line?

Answer 8

Centre of the myosin

Question 9

What is the Z line?

Answer 9

Centre of actin which defines where the sarcomere is

Question 10

Describe the structure of smooth muscle?

Answer 10

Look of visible cross striations

- cells are much smaller than skeletal muscle fibres (30-200 microns compared to up to 30 cm)

Question 11

What is the primary control of smooth muscle contraction?

Answer 11

Control of the autonomic nervous system

Question 12

Describe the structure of Multi-unit smooth muscle

Answer 12

Each individual smooth muscle cell has a direct innervation, continuous activity (tonic activity) - arteries and arterioles

Question 13

Describe the structure of single-unit smooth muscle

Answer 13

Greater number of gap junctions between each other, do not require individual innervation

Question 14

How to tell the difference between relaxed and stimulated smooth muscle cells?

Answer 14

Stimulated = Ovoid cell 
Relaxed = spindle shaped cell

Question 15

What are the components of skeletal muscle?

Answer 15

Epimysium = covers the whole muscle 
Perimysium = covers fascicle 
Endomysium = basement membrane and extracellular matrix 
Sarcolema = muscle cell membrane

Question 16

How to identity syncitial cells from a histology slide?

Answer 16

Multinucleated

Question 17

What nerve is each muscle fibre innervated by?

Answer 17

Nerves from motor neurones - cell bodies in ventral part of the spinal cord

Question 18

Describe the structure of the neuromuscular junction

Answer 18

Specialised structure

• mitochondria can be seen in the end of the nerve terminal
• underneath cell membrane = highly modified muscle cell membrane which with the nerve terminal forms the motor end plate
• circular objects = synaptic vesicles

Question 19

Describe the structure of the muscle fibre membrane

Answer 19

• Many receptors for the extracellular matrix proteins
• Alpha dystroglycan highly glylosylated peripheral membrane
• Integrins - heterodimeric transmembrane proteins that mediate cell-matrix as well as cell-cell adhesion. specific forms in muscle:
• substrate specificity is determined by 𝛂 subunit specificity e.g. 𝛂7𝛃1 heterodimer is the major laminin-binding integrin in muscle (𝛂7𝛃1-laminin 2 in muscle)

Question 20

What is the extracellular matrix made up of?

Answer 20

Lots of type 4 collagen, lamins, proteoglycan perlelcan and other molecules
- allows muscle fibres to exist in a harmonious state

Question 21

What is myogenesis?

Answer 21

formation of muscular tissue, particularly during embryonic development
- somite = dermatome, sclerotome, epaxial (produces muscles of the back) and hypaxial (produces muscles of the flank, thorax, abdomen and limbs) myotome

Question 22

What role do muscle progenitor cells play in the formation of myotube?

Answer 22

1. Muscle progenitor cells are shed from myotome and migrate to muscle formation sites
2. Once close differentiate into myoblasts
3. Committed myoblasts
4. Fuse to form a myotube

Question 23

What occurs when PAX 3&7, myoD & myogenin are absent in the formation of myotube?

Answer 23

myoD and Myogenin are the muscle determining genes also transcription factors
- absence of both leads to deficit in skeletal muscle

Question 24

What is myogenesis controlled by?

Answer 24

Coordinated expression of muscle specific transcription factors
In 1st round, myoblasts line up and fuse to form primary muscle fibres
Primary muscle fibre is used as a scaffold for formation of secondary myofibres

Question 25

Which myogenic factors control skeletal muscle formation at which sites?

Answer 25

All muscle cells express a core set of myogenic factors e.g. Myogenic factor 5 (MYF5) muscle specific regulatory factor 4 (MRF4). myoblast determination protein (MYOD) and myogenin, which are required for myogenic differentiation
- other transcription factors reflect linage - specific differences and are necessary for the activation of myogenic factors and/or proliferation and survival of muscle progenitor cells

Question 26

What are satellite cells?

Answer 26

A muscle stem cell

• develop at the same time as myotubes
• closely attached to the muscle fibre but not a part of it

Question 27

How does longitudinal growth of muscle fibres occur?

Answer 27

Sarcomeres are added to the ends of muscle fibres with fusion of myogenic cells produced by satellite cells

Question 28

How does transverse growth of muscle fibres occur?

Answer 28

Fusion of the myogenic cells produced by satellite cells along the length of the fibre

Question 29

What does muscle fibre damage cause?

Answer 29

segmental necrosis

Question 30

How is segmental necrosis repaired?

Answer 30

Satellite cell activation, differentiation and fusion
- in response to damage satellite cells divide and produce myoblasts which fuse with the muscle fibre or enter the empty space left by damage and fuse together in a very similar pattern to development
One cell must assume a quiescent state as a replacement

Question 31

What is muscular dystrophy?

Answer 31

Caused by mutations in genes encoding for proteins of:
- extracellular matrix - absence of lamin-𝛂2
- muscle fibre membrane (sarcolema)
- contractile apparatus
- Cytoskeleton - beneath the membrane, anchoring myofibrils
Characterised by necrosis and a failure to adequately regenerate muscle