Neuromuscular Disorders

Question 1

What is Malignant Hyperthermia?

Answer 1

• inherited autosomal dominant disease of overheating and increased metabolic rate.

Genes affected are:

1. Ryanodine (RyR1) - allows calcium stores to be released to SR
2. Dihydropyridine (DHPR) - voltage sensor for RyR1
3. Calsequestrin (CSQ) - calcium storage protein in SR

Question 2

Explain the steps involved in excitation-contraction coupling. ❗️

Answer 2

Sodium in —> voltage receptors triggered —> release CA2+ —> troponin deactivates tropmyosin and exposes actin sites —> contraction —> removal of Ca2+ —> tropomyosin restored —> contraction stops

1. Net entry of sodium initiates action potential down sarcolemma and T-tubules
2. This activates voltage sensitive receptors which triggers CA2+ release into cytosol.
3. Calcium ions bonds to troponin which changes its shape —> removes blocking action of tropomyosin, exposing actin active sites.
4. Contraction occurs when myosin heads attach and detach from actin. This pulls actin filaments into center of sarcomere. ATP hydrolysis powers the cycling
5. Removal of Ca2+ by active transport into SR.
6. Tropomyosin blockage restored and blocks myosin sites on actin. Contraction ends and muscle relaxes h

Question 3

What are the different types of Limb-Girdle Dystrophies

Answer 3

Sarcoglycan Associated: LGMD2D to F

Caveolin 3: LGMD1C

Dysferlin: LGMD2B

Calpain-3: LGMD2A - Calpain is a CA2+ dependent protease —> muscle repair

Question 4

What are the 3 types of fatigues?

Answer 4

1. High frequency fatigue- running to catch the train; 98% initial level in 1 min; membrane repolarisation not so effective which give you high frequency fatigue
2. Metabolic fatigue - end of basketball game; less force due to less CA2+ release and decrease in force development by myofibrils; low ATP levels —>less activation of RyR; increase in Mg2+
3. Long duration fatigue - eccentric exercise;