Recent advances in skeletal muscle physiology

Question 1

Muscle Contraction

Answer 1

Action Potential from a-motor neurone fibre reaches neuromuscular junction -> ACh is released into the synapse and binds to nACh receptors on the post-junctional sarcolemma -> Induces a motor end plate potential which activates Voltage-gated Na channels.

Na release activates Voltage-gated Ca channels in the t-tubular membrane -> Intracellular Ca is released from the sarcoplasmic rectilium -> Ca binds to troponin C causing a conformational change in the troponin complex exposing myosin binding site on actin -> myosin and actin bind and the myosin head pulls the actin chain to cause shortening of the sarcomere and muscle contraction. THis process is ATP dependent

Question 2

Energy sources in skeletal muscle

Answer 2

• ATP from aerobic metabolism and anaerobic metabolism
• Creatine phosphatase + ADP - breaks down to produce ATP and creatinine

Question 3

Pathophysiology of Malignant Hyperpyrexia

Answer 3

• Ryanodine receptor 1 gene mutation (possibly also Cav1.1 and STAC3 proteins)
• Exposure to volatile anaesthesia or suxamethonium
• Persistently open RYR1 channels leading to high levels of Ca available to the muscle
• Causing sustained muscle contraction with no relaxation
• Leads to heat production, rhabdomyolysis and muscle contractures
• It is thought dantrolene works by binding to and closing the open RYR1 channel