Determinants of muscle fiber phenotype and Neuromuscular junction for skeletal muscle

Question 1

What are the 4 determinants of muscle fiber phenotype for skeletal muscle?

Answer 1

1. Cell lineage
2. Nerve-evoked electrical activity
3. Mechanical conditions
4. Paracrine, autochrome, and hormones

Question 2

How does cell lineage determine muscle fiber phenotype?

Answer 2

• During embryonic development, all 3 muscles (skeletal cardiac smooth) are originated from the somatic mesoderm.
• Myoblasts (progenitor) originates from the somatic mesodermal germ layer and will migrate out to form phenotypic muscle fibers.

Question 3

How is the date of myocytes determined once they leave the somites?

Answer 3

• Coelomic graft model
  Myoblasts start migrating from the lumbosacral somites into the chick hindlimb bud occur between stages 16 to 20
• A section of graft hindlimb bud was removed between stages 16 to 18 then was placed into the coelomic cavity of host embryo and retrieved at stages 30 to 33

Question 4

What happens when mammalian muscle are transported and made to regenerate in a different body location?

Answer 4

• Some of the information determining fiber type is apparently derived from the muscle of origin rather than from the new position

Question 5

What are satellite cells?

Answer 5

• Can be found lying between the basal lamina and plasma membrane of muscle fibers
  Aka myosatellite cells Normally inactive but activated after muscle injury or in response to intensive physical exercise Fuse among themselves to make new muscle fibers or fuss with damaged muscle fibers to repair damage (keeps same muscle type)

Question 6

What can a single avian or rodent satellite cell transform into?

Answer 6

• A single avian or rodent satellite cell can only transform into either fast or slow MyHC isoform, not both
• Satellite cells derive from new myoblasts which that fused into forming multi-nucleated myotubules that express a MyHC type similar to the fiber from which the satellite cells were derived

Question 7

What has satellite cell behaviour been noticed in humans?

Answer 7

Satellite cell from human is homogeneous in nature (single satellite cell has ability to transform itself into a muscle fiber with either fast or slow MyHC isoform.

Question 8

What is nerve-evoked electrical activity with muscle fibers?

Answer 8

External signals can change muscle phenotype in adult
When a nerve from a fast muscle is transplanted to a slow muscle (& vice versa) both the re-innervated muscles change phenotype according to the new nerve supply

Question 9

What is the pattern of electrical activity evoked in fast and slow muscles?

Answer 9

• In type I motor units, they seem to receive high amounts of impulses delivered in long low-frequency sequences
  (Low frequency activity has been superimposed on normal activity leading to fast to slow transformation)
• In type II motor units, they receive short bursts of high-frequency activity

Question 10

What are the problems with in Vivo slow to fast transformation studies?

Answer 10

• Exogenous activity (nerve stimulation studies) is superimposed on activity from the central nervous system (this limits pattern control)
  Since the external activity is always added, the effect of a reduced amount of activity can not be studied in innervated muscles as a control

Question 11

How does mechanical condition (stress) help determine muscle fiber phenotype?

Answer 11

• Depolarization leads to shortening and/or mechanical tension in muscle
  Believed contraction against a large resistance leads to larger muscles mass than contraction against a lower resistance
  Use hind limb suspension study (rats lifted by rail so unload hind limbs leading to atrophy, initially also there is a halt in electrical activity indicated by an integrated electromyogram (EMG))
• Changes in muscle usage will transform muscle phenotype

Question 12

What happens in the hindlimb suspension test when there is an initial halt in electrical activity indicated by the EMG?

Answer 12

• The integrated EMG appears to gradually recover to normal levels within a few days where as muscle atrophy continues to progress
• This could mean that the action potential activity is of relatively little importance
  A more important role should be postulated for force generation per se

Question 13

What are the 3 major conditions regulating size of muscle?

Answer 13

• The number of nuclei- increase nuclei, implies your satellite cells have fused with your muscle fibers, make it bigger, hypertrophic
• The rate of protein synthesis for each nucleus
• The rate of protein degradation

Question 14

What is myostatin? What happens when it’s disrupted?

Answer 14

• Member of the trans-transforming growth factor β(TGF-β) superfamily
  Stops your muscles from growing (don’t become monster) inhibitor of muscle growth
• Disruption of myostatin gene leads to development of grossly enlarged muscles
  Hyperplasia (increase number of fibers) and hypertrophy (increase fiber size) combine for enlargement

Question 15

What is the insulin-like growth factor I (IGF-1)?

Answer 15

• Works as local hormone that promotes hypertrophy in adult animals
  In muscle tissue, IGF increases myotube diameter, suppressed proteolysis, stimulate protein synthesis, and induce a higher number of nuclei per length of myotube
• Also increases DNA content in muscles

Question 16

What is the motor end plate? What do muscles for fine co trip have fewer of?

Answer 16

• Structure where axonal branches of a motor neuron form contact to a group of target muscle fibers within a single motor unit through presynaptic buttons
• Muscle for fine control will have fewer muscle fibers per motor unit

Question 17

What factors have the potential to serve as messengers?

Answer 17

• Free intracellular Ca2+
• Metabolites (lipids, ADP, ect)
• Hypoxia.
• Tension.

Question 18

Regulation of force is mainly a question of regulating fiber size:

Answer 18

• Size can be achieved by regulating three major conditions:
• The number of nuclei.
• The rate of protein synthesis for each nucleus.
• The rate of protein degradation.

Question 19

What is primary and secondary synaptic cleft?

Answer 19

Primary - synaptic button that occupies a depression.

Secondary - synaptic cleft is the sarcolemma of the muscle fiber that forms the infolding deep junctional fold.

Question 20

What is the pathway from CNS to muscle contraction?

Answer 20

• Electrical signal (impulse/action potential) from CNS
• Through motor neurons (nerve)
• At junction between motor neuron and skeletal muscle where electrical transforms into chemical neurotransmission
• Chemical is then transformed in electrical in outer membrane of muscle fiber
• Electrical is then transformed to mechanical in muscle fibers for muscle contraction.

Question 21

What is the sequence of events for chemical synapse for ligand gated channels?

Answer 21

• Impulse (electrical) arrived at presynaptic terminal
• Depolarization at membrane activates voltage gated Ca Channels (Ca influx)
• Increase in cytosol Ca triggers exocytosis of synaptic vesicles
• Release of neurotransmitters (chemical) to synaptic cleft
• Binding of neurotransmitters to receptors at postsynaptic plasma membrane cause Ligand-gated Na channels to open
• If change in membrane potential is sufficient to reach threshold, action potential is generated.

Question 22

What is enclosed by membrane bound synaptic vesicles located at presynaptic terminals?
How do synaptic vesicles attach to presynaptic terminals?

Answer 22

• Neurotransmitter acetylcholine (ACh)
• Synaptic vesicles contain vesicular docking proteins that allow them to attach at presynaptic terminals rich in membrane docking proteins.

Question 23

What degrades acetylcholine (ACh)?

Answer 23

• Enzymatically degraded by acetylcholinesterase (AChE) located on the postsynaptic membrane
• AChE terminates the signal by hydrolyzing ACh to form choline and acetyl CoA
  Cholinebis reuptake back to presynaptic terminal and recycled back into forming ACh by choline acetyltransferase

Question 24

What is axonal transport? Two types?

Answer 24

• Axonal transport requires axonal cytoskeleton, motor proteins (kinesin and dynein), and hydrolysis of ATP
• Anterograde is kinesin-mediated that carries cargos from soma toward axon terminal
• Retrograde is dynein-mediated that carriers cargos from axon terminal to soma

Question 25

How does axonal transport help rabies?

Answer 25

• Viral particles migrate by retrograde transport to replicate within neurons
  Rabies virus is also transported by anterograde transport by peripheral nerves to salivary glands (how we get it from biting)

Question 26

How does axonal transport affect tetanus toxin?

Answer 26

• Use retrograde transport to enter CNS.

Question 27

How does axonal transport affect shingles?

Answer 27

Zoster virus enters into nerve body using retrograde transport
Virus is then reactivated and move to the nerve ending using anterograde transport

Question 28

How does neuromuscular transmission affect botulinum toxin?

Answer 28

• Exotoxin from bacterium prevents release of acetylcholine at the presynaptic terminal (cause muscle paralysis and dysfunction of autonomous nervous system)

Question 29

What is type I and type IIb muscle you’d find in either a marathon runner or sprinter runner?

Answer 29

• Type I muscle would be in marathon runner (endurance)
• Type IIb would be in sprinter runner (force and speed)

Question 30

How does neuromuscular transmission affect myasthenia gravis?

Answer 30

• Has antibodies that are against acetylcholine receptors
  Prevents binding of acetylcholine to the nicotinic acetylcholine receptors on postsynaptic membrane
  Blocks normal nerve muscle interaction.