SKELETAL MUSCLE: MUSCLE FATIGUE & PLASTICITY

Question 1

Give the colloquial definition for fatigue

Answer 1

reduction in physical or mental performance

Question 2

Give the physiological definition(s) for fatigue

Answer 2

• failure to maintain the required or expected force (isometric contractions)
• failure to maintain force, power, or velocity (dynamic contractions)

Question 3

Give the definition for submaximal fatigue

Answer 3

Increased effort required to maintain submaximal task

Some fibres become fatigued and less able to generate force (power), additional motor units recruited in order to achieve the same task – e.g. to run a steady pace in a marathon

Question 4

Describe the CNS pathway from the brain to the muscle fibres

Answer 4

Input from brain and higher centers → ventral horn → cell body → ventral root → motor nerve → muscle fibres

Question 5

Differentiate between central and peripheral fatigue

Answer 5

Skeletal muscle fatigue
- metabolic byproducts are key factors
- function of motor units may also be at play
- could be do to failure in one of or a few of these: NMJ, sarcolemma, T-tubules, voltage sensors, RyR1, CaV1.1, SR Ca2+ availability, Ca2+ binding and actin-myosin interaction.

Central fatigue
- Failure in: Premotor cortex, motor cortex, descending pathways, and/or motor neuron activation/inhibition
- reduced excitatory drive from the motor cortex
- Presynaptic inhibition may be increased via decreased firing of muscle spindles
- Neural factors: serotonin (5-HT), dopamine (DA), nor-adrenaline (NA), play an important role during exercise
- Central fatigue hypothesis states that exercised-induced changes in these neurotransmitters (NTs) lead to CNS fatigue

Question 6

How can we measure central fatigue to rule out whether there is central fatigue or peripheral fatigue at play?

Answer 6

twitch interpolation

Question 7

Describe the tetanus stress graph over time during peripheral fatigue and the factors at play

Answer 7

Phase 1: rapid fall

Phase 2: slower decline

• Rapid decline due to fatigue of Type II fibres (Type I are fatigue resistant)
• Paralleled by depletion of glycogen, CrP; increased intracellular H+ and lactic acid
• Decreased pH alters Ca2+ binding to TnC, as well as actin-myosin interactions
• Increased phosphate accumulation ([Pi]) (2 mM at rest to 40 mM with exercise) exerts effects via Ca2+ release, Ca2+ sensitivity, actin myosin binding

Question 8

True or false: Fatigue is the result of depleted energy stores

Answer 8

False! ATP is always present at sufficient levels, thus not a contributing factor to fatigue

Question 9

Describe twitch interpolation technique

Answer 9

• Subject performs a maximum voluntary contraction (MVC). Partway through, a maximal electrical stimulation is used to elicit a twitch. If force increases during this interpolated twitch, this demonstrates that the muscle was capable of generating extra force, and the poor force during the MVC was due to reduced motor drive from the CNS.
• Even at rest many subjects are unable to fully activate their muscles voluntarily. Trained athletes are better at recruiting entire motor unit pools.

Question 10

Explain how K+ contribute to peripheral fatigue

Answer 10

During periods of high activity, potassium concentration increases in the t-tubule. The resting muscle membrane potential is now altered and less negative. This impairs the ability of muscle cells to respond to further action potentials as it is now harder for muscle cells to depolarize.

Question 11

Explain how Ca2+ contribute to peripheral fatigue

Answer 11

The change in membrane potential caused by increased extracellular K+ causes a decrease in the release of Ca2+ from the sarcoplasmic reticulum. Reduced calcium release can lead to weaker contractions and decreased force generation.

Question 12

Discuss the effects of PGC1 on fatigue

Answer 12

PGC1: transcriptional coactivator involved in the regulation of energy metabolism and mitochondrial biogenesis (the process by which more mitochondria are made )
- Increased mitochondrial content improves the cell capacity to generate ATP.
- Delays the onset of fatigue by increasing energy supply.

Question 13

What regulates PGC-1 expression?

Answer 13

Exercise! Exercise activates AMP-activated kinase (AMPK) which stimulates PGC-1a expression.

Question 14

What comes first for pre-skeletal muscle fibres? innervation or differentiation into muscle fibres?

Answer 14

differentiation

Question 15

Fill in the blank: Fibers innervated with Type I motor neurons become ______ motor units
Fibres innervated with Type II motor neuron become ______ motor units

Answer 15

• slow oxidative
• fast

Question 16

Describe different types of muscle growth and how it impacts force, velocity, and shortening capacity

Answer 16

1. more sarcomeres in parallel; caused by either hypertrophy or hyperplasia
   - force: doubles
   - velocity: no change
   - shortening capacity: no change
2. more sarcomeres in series;
   - force: no change
   - velocity: doubles
   - shortening capacity: doubles

Question 17

Define: hypertrophy

Answer 17

Hypertrophy: enlargement of muscle fibres

Results in increase in strength and diameter

Question 18

Define: hyperplasia

Answer 18

Hyperplasia: increase in number of muscle cells; Results in more sarcomeres in parallel.

Question 19

Explain the mechanism underlying muscle atrophy

Answer 19

Disuse of muscles lead to inhibition of protein synthesis which stimulates protein degradation via a complex molecular pathway.

FOXO is activated which leads to the transcription of atrogin and other atrophy-related genes.

Atrogin and MuRF are both ubiquitin ligases which tag proteins with ubiquitin.

Ubiquitin marks proteins for destruction and is thus responsible for myocyte protein degradation.

Question 20

Explain how anabolic steroids can affect muscle fibres and hormone disturbances

Answer 20

• increase protein content of muscle fibres leading to hypertrophy
• however, anabolic steroids also enhance negative feedback loops resulting in lower LH
  levels
• lower LH levels mean less LH acting on leydig cells which produce testosterone.
• sertoli cells produce androgen binding proteins (ABP) which concentrate testosterone in the seminiferous tubules.
• lower levels of intratesticular testosterone mean less testosterone for ABP to bind to resulting in reduced spermatogenesis.
• so, anabolic steroids result in smaller testosterone and lower sperm count in men.

Question 21

Discuss muscle plasticity

Answer 21

When a nerve is removed from a muscle, it is considered denervated. The muscle will attempt to be reinnervated by either the same nerve fibre or another one.

If a muscle is reinnervated by a different by a different motoneuron type, the muscle will take on new properties.

For example, a type II muscle that is reinnervated with a type 1 motoneuron will have a slower shortening velocity