Origins of skeletal muscle
Muscle forms from the somites (paraxial mesoderm) Sclerotome (bone, ribs, cartilage) Myotome (muscle precursors) Dermomyotome (myotome and dorsal dermis) Syndetome (tendons)
Paracrine factors induce Myf5 and MyoD = myogenic commitment (myoblasts)
Myoblast proliferate (Growth Factors)
Cell cycle exit, Myogenin expression= Terminal differentiation
Structural proteins expressed and myotubes form.
Myotubes align and fuse
Biphasic muscle development: Primary and Secondary fibres
Satellite cells: regeneration and postnal growth (muscle stem cells)
Embryonic fibre number
Fibre number is generally set at birth
Fibre number can be affected by temperature, hormones, nutrition and innervation. Affect MRF expression duration
Postnatal muscle growth hypertrophy
After birth, an increase in muscle mass due to an increase in fibre size (hypertrophy)
Muscle Stem Cells (MuSCs) called Satellite cells. Undifferentiated muscle precursors, self-renewing.
MuSCs proliferate and incorporated into muscle fibres. Return to quiescence when not needed.
Muscle fibres are multinucleated. Maintain cytoplasm: nuclei ratio,
Type 1 fibre
Back extensor • Vitrually inexhaustible • High mitochondria – aerobic • Extensive blood supply and abundant myoglobin • Oxidative phosphorylation
Type 2 fibre
- Fatigues easily
- Few mitochondria: mainly anaerobic metabolism
- Glycolytic (type a or b)
- Poor vascularization and lack myoglobin
The effects of training on fibre type
- Untrained individuals 50:50 ratio of fast (IIA and IIX) to slow (I) twitch fibres
- Long and middle distant runners: 60-70% slow
- Sprinters: 80% fast-twitch
- Sports requiring greatest aerobic and endurance capacities: slow muscle up to 90-95%.
- Sports with greater anaerobic capacities (strength and power) have fast muscle from 60-80%
The marathon runner
- Muscles small but fatigue resistant
- Muscle dense and strong for their size High oxidative capacity of muscles
- Work over very long periods of time
- Not explosive strength
Muscles adapted for explosive release of force:
- Rapid powerful contractions
- Easily fatigued at maximum effort
- Low oxidative capacity via mitochondria
- High force per cross-sectional area of muscle
Muscle adapted for immense strength:
- Muscles are hypertrophied
- Highly glycolytic
- Fatigue easily
- High muscle to total body mass ratio
- Muscle size beginning to interfere with locomotion
Powerlifter vs sprinter
- 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.
Fibre- type diversification
All vertebrate sarcomere structure the same
Molecular variability depending on function
Multiple isoforms of myofibrillar proteins: Alternative splicing or promoters
> 3000 genes differentially expressed between males and females skeletal muscle.
Differences in myosin isoforms
Type I ♂: 36% ♀:44% (slow)
Type IIA ♂: 41% ♀:34% (fast)
♂: larger fibre cross sectional areas (CSA) compared to women
Primary male sex hormone: required for the development of the male reproductive system
Promotes secondary sexual characteristics: muscle + bone mass, body hair, deep voice
What does testosterone promote
Promotes the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibit adipogenesis. (androgen receptor mediated pathway)
Stimulates: satellite cell replication, muscle protein synthesis, fibre hypertrophy
Pax3 establishes MuSCs identity during embryonic development , expressed in the presomitic mesoderm, required for survival of the ventro-lateral dermomyotome, which gives rise to the hypaxial and limb musculature
Pax7 establishes MuSCs during late foetal and perinatal growth
Pax7 null mice are deficient in the number of MuSCs and fail to regenerate muscle after injury in adult mice
Why is Pax 3 and Pax 7 important?
Pax 3 and 7 are required for MuSC formation and regeneration
3 stages of regeneration
3 main phases:
A) Degeneration/inflammation phase: (first few days)
Myofibre rupture and necrosis, formation of hematoma, inflammatory response.
B) Regeneration Phase: 4-5 days pi.
Phagocytosis of damaged tissue, SC activation and proliferation,
C) Remodeling phase: 2/3 wks
maturation of regenerated myofibers, restoration of blood supply and innervation, recovery of muscle functional capacity and also fibrosis and scar tissue formation.
- Sarcopenia: age related loss of muscle mass
- 3-8% decrease per decade after the age of 30, higher after 60
- 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
- Biochemical and metabolic changes: mitochondrial mutations, reduced oxidative and glycolytic enzyme activity
- Reduced endocrine function, reduced physical activity
a cell commitment to a myogenic lineage, but not yet differentiated.
Myogenic Regulatory Factors
Transcription factor required for commitment and terminal differentiation of muscle cells.
Satellite cells -
divide and serve as a source of new myonuclei during postnatal growth. They contribute to the growth of the fibres and participate in the regeneration process.
produce slow maintained contractions that are virtually inexhaustible.
generates high force contractions that fatigue easily.
increase in muscle mass due to increase in fibre size
increase in the number of muscle fibres.
age-related loss of muscle mass