26.5.2: Muscle disease

Question 1

What type of protein does Ca interact with at the neuromuscular junction, where the end result is acetylcholine release?

Answer 1

SNARE proteins

Question 2

What does calcium bind to in order to begin muscle contraction?

Answer 2

Troponin

Question 3

Which organelle without the cell is key to the movement of Ca within the cell?

Answer 3

Sarcoplasmic reticulum

Question 4

Which muscle metabolism system is used in high intensity, short duration exercise?

Answer 4

Phosphagen system (this consists of creatine kinase stores and the myokinase system)

Question 5

What is the main energy source in muscle cells?

Answer 5

Glycogen

Question 6

Which energy source(s) is important for muscle in sustained exercise?

Answer 6

• Fatty acids
• Branched amino acids (produced from gluconeogenesis and the TCA cycle)

Question 7

Which type of fibres are used for aerobic activity? What is their major storage fuel and contraction time?

Answer 7

Type I muscle fibres
* Contraction time = slow
* Resistance to fatigue = high
* Used for = aerobic activity (max. = hours)
* High oxidative capacity and mitochondrial density
* Major storage fuel = triglycerides

Question 8

Which types of muscle fibres are used for short term anaerobic activity? What is their contraction time and major storage fuel?

Answer 8

Type II x fibres
* Contraction time = fast
* Moderate resistance to fatigue
* Used for short term anaerobic activity (<5 mins max)
* High power produced
* Medium mitochondrial density
* Major storage fuels = ATP, creatine phosphate, small amounts of glycogen

Question 9

Which has higher capillary density: Type I or Type IIx muscle fibres?

Answer 9

Type I (these fibres have higher oxidative capacity than Type IIx)

Question 10

Horses are great athletes, so they have a higher muscular oxidative capacity. What does this mean? What are the implications of this?

Answer 10

• Higher mitochondrial mass
• Higher aerobic enzymatic pool

Implications of this -> possibility for oxidative stress with products produced from multiple metabolic pathways

Question 11

Which products of metabolic reactions in muscles result in oxidative stress? What can these lead to?

Answer 11

• Reactive oxygen species (ROS) from the mitochondrial respiration chain
• Acetyl-carnitines from fatty acid oxidation
• Lactate in glycolysis

These can result in sarcolemma instability and the release of CK, AST and troponin.

Question 12

What mechanisms exist to counteract oxidative stress? Specify which pathway each acts on.

Answer 12

• Vitamin E - sarcolemma repair
• Cysteine - respiratory chain, ROS
• Q10 - reactive species produced from TCA cycle, amino acid and fatty acid oxidation

Question 13

If excess lactate is produced, and there is not sufficient oxygen present, what is the end result?

Answer 13

Acidosis

Question 14

What are the plasma markers of muscle damage and where is each released from in the myofibre (muscle cell)?

Answer 14

• Creatine kinase (CK) - released from sarcoplasma and mitochondria
• Aspartate-transaminase (AST) - released from sarcoplasm
• Troponins - released from sarcoplasm
• Acetyl-carnitines - released from sarcoplasm and mitochondria

Question 15

True/false: we can modify the proportion of muscle fibres in a given muscle by breeding.

Answer 15

True

Question 16

Elevated acetyl-carnitines might indicate what?

Answer 16

• Muscular metabolic derangements
• Seen with toxic and genetic myopathies

Question 17

Post-exercise, you might see elevation of which plasma markers of muscle damage?

Answer 17

• Creatine kinase (CK)
• Aspartate-transamine (AST)
• Troponins

This is normal - moderate-high intensity exercise will cause an increase. Need to consider the horse’s exercise history and how high the levels are.

Question 18

This graph shows the levels of enzymes in the blood after muscle damage. Which enzyme is indicated by 1 (blue line)?

Answer 18

Creatine kinase (CK)

Question 19

This graph shows the levels of enzymes in the blood after muscle damage. Which enzyme is indicated by 2 (orange line)?

Answer 19

AST

Question 20

Where does PSSM-1 affect in the muscle fibre?

Answer 20

• Affects glycogen synthase
• This means glycogen is stored improperly
• When it needs to be lysed to provide energy, the enzyme cannot recognise and bind to this poorly stored glycogen

Question 21

What is PSSM-1?

Answer 21

Polysaccharide storage myopathy
* Genetic mutation in GY1
* The glycogen synthase enzyme is constantly turned on
* This means the enzyme gets overwhelmed
* Glycogen is not properly formed in the organised way -> this means it cannot be lysed by the relevant enzyme when needed
* Therefore, there is plenty of glycogen, but because it has been improperly stored, it cannot be utilised

Question 22

What is PSSM-2?

Answer 22

Polysaccharide storage myopathy
* This is a large group of muscule conditions that see some accumulation of glycogen
* There are likely different aetiologies/mutations involved
* This group used to include myofibrillar myopathies but these are now classified separately

Question 23

Clinical signs of PSSM-1

Answer 23

• Reluctance to move forward
• Poor performance
• Sweating
• Possibly more severe clinical signs e.g. myoglobinuria

Question 24

Clinical signs of PSSM-2

Answer 24

• More subtle clinical signs -> poor performance mostly
• Lack of engagement from hindquarters
• May see mild elevation of muscle enzymes post-exercise

Question 25

What is myofibrillar myopathy?

Answer 25

• Type of exertional myopathy
• Abnormal desmin protein is unable to support the Z-disc
• There is contractile apparatus dysfunction -> fibrillar rupture