WEEK 11 (Muscle damage and Repair) Flashcards
What are the causes of Skeletal muscle injury?
- Direct trauma (e.g lacerations & contusions)
- Strains
- Degenerative diseases (e.g muscle dystrophies)
Describe how skeletal muscles regenerate
COMPLETELY and SPONTANEOUSLY in response to minor injuries (e.g strain) but after severe injuries muscle healing is incomplete often resulting in the formation of FIBROTIC TISSUE that impairs muscle function
Why is the destruction of striated muscle fibers damaging?
Since the remaining healthy fibers cannot divide to replace the damaged ones
Describe the importance of Satellite cells
- Skeletal muscles have stem cells called SATELLITE CELLS
- Located between the SARCOLEMMA (plasma membrane) and the ENDOMYSIUM (basement membrane)
- Activated at the site of muscle injury to differentiate into myoblasts that can fuse with the damaged muscle fibers. If the damage is more extensive, a number of satellite cells can form myoblasts that fuse to produce new muscle fibers which grow thicker by the fusion of additional myoblasts
When does muscle regeneration occur?
When intense resistance training injures muscle fibers
What must happen when muscles hypertrophy/grow larger as a result of increased fiber thickness?
The number of nuclei in each fiber must increase in proportion to the larger volume of the fiber
[these new nuclei are provided by the satellite cells]
What state are Satellite cells normally in?
QUIESCENT (resting) state where their cell cycle is reversibly arrested until they are stimulated to divide and differentiate into myoblasts
What happens to Satellite cells once they age?
With advanced age, Satellite cells change from a REVERSIBLE QUIESCENT state to an IRREVERSIBLE SENESCENT state in which they are unable to replenish themselves or repair muscles
What does advanced ageing of Satellite cells lead to?
SARCOPENIA (a loss of muscle mass) and an accompanying loss of strength
What is Sarcopenia promoted by?
- Decreased ability to remove defective mitochondria through autophagy
- Reduced generation of new functional mitochondria
How has exercise helped the effects of Sarcopenia?
Exercise induces the production of new mitochondria and has been shown to partially reverse the senescent decline in muscle mass and strength
What is Myostatin?
A cytokine in skeletal muscles that acts in an autocrine fashion to suppress skeletal muscle growth
What happens when the gene for myostatin is “knocked out” in mice and cattle?
The animals experience greatly increased muscle growth due to:
- increased numbers of myofibers formed during embryonic development
- enhanced satellite cell function and hypertrophy of myofibers after birth
What is the connection between Satellite cell function and Myostatin?
Satellite cell function is regulated by Myostatin
What are the three muscle proteins required for the formation of new sarcomeres and consequent growth of myofibrils within the muscle fiber?
- Titin
- Nebulin
- Obscurin
What is Titin?
An extremely long protein that spans half the length of the sarcomere with its amino-terminal end anchored in one of the Z-discs on each side of the sarcomere and its carboxyl-terminal end in the M-band. It provides ELASTICITY and STABILISES myosin.
What are the properties of Nebulin?
- Helps align actin
- Found within the actin of the I bands
- Needed for the globular actin proteins to assemble into thin filaments of the appropriate length for the muscle
Where can Obscurin be found?
Surrounding the sarcomeres primarily around the Z-discs and M-bands
What do Titin, Nebulin and Obscurin serve as?
Molecular scaffolding for the formation of new sarcomeres during muscle growth and repair
What is the function of Obscurin?
Helps the myosin proteins assemble into the A bands
What are the functions of Titin?
- Scaffolding
- Muscle elasticity
- Unfolding and developing passive tension when a muscle is stretched
