26.5.2: Muscle disease Flashcards
What type of protein does Ca interact with at the neuromuscular junction, where the end result is acetylcholine release?
SNARE proteins
What does calcium bind to in order to begin muscle contraction?
Troponin
Which organelle without the cell is key to the movement of Ca within the cell?
Sarcoplasmic reticulum
Which muscle metabolism system is used in high intensity, short duration exercise?
Phosphagen system (this consists of creatine kinase stores and the myokinase system)
What is the main energy source in muscle cells?
Glycogen
Which energy source(s) is important for muscle in sustained exercise?
- Fatty acids
- Branched amino acids (produced from gluconeogenesis and the TCA cycle)
Which type of fibres are used for aerobic activity? What is their major storage fuel and contraction time?
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
Which types of muscle fibres are used for short term anaerobic activity? What is their contraction time and major storage fuel?
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
Which has higher capillary density: Type I or Type IIx muscle fibres?
Type I (these fibres have higher oxidative capacity than Type IIx)
Horses are great athletes, so they have a higher muscular oxidative capacity. What does this mean? What are the implications of this?
- Higher mitochondrial mass
- Higher aerobic enzymatic pool
Implications of this -> possibility for oxidative stress with products produced from multiple metabolic pathways
Which products of metabolic reactions in muscles result in oxidative stress? What can these lead to?
- 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.
What mechanisms exist to counteract oxidative stress? Specify which pathway each acts on.
- Vitamin E - sarcolemma repair
- Cysteine - respiratory chain, ROS
- Q10 - reactive species produced from TCA cycle, amino acid and fatty acid oxidation
If excess lactate is produced, and there is not sufficient oxygen present, what is the end result?
Acidosis
What are the plasma markers of muscle damage and where is each released from in the myofibre (muscle cell)?
- 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
True/false: we can modify the proportion of muscle fibres in a given muscle by breeding.
True
Elevated acetyl-carnitines might indicate what?
- Muscular metabolic derangements
- Seen with toxic and genetic myopathies
Post-exercise, you might see elevation of which plasma markers of muscle damage?
- 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.
This graph shows the levels of enzymes in the blood after muscle damage. Which enzyme is indicated by 1 (blue line)?
Creatine kinase (CK)
This graph shows the levels of enzymes in the blood after muscle damage. Which enzyme is indicated by 2 (orange line)?
AST
Where does PSSM-1 affect in the muscle fibre?
- 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
What is PSSM-1?
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
What is PSSM-2?
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
Clinical signs of PSSM-1
- Reluctance to move forward
- Poor performance
- Sweating
- Possibly more severe clinical signs e.g. myoglobinuria
Clinical signs of PSSM-2
- More subtle clinical signs -> poor performance mostly
- Lack of engagement from hindquarters
- May see mild elevation of muscle enzymes post-exercise
What is myofibrillar myopathy?
- Type of exertional myopathy
- Abnormal desmin protein is unable to support the Z-disc
- There is contractile apparatus dysfunction -> fibrillar rupture
