Muscle structures and pathologies

Question 1

What are the features of type 1 muscle fibres?

Answer 1

Slow twitch
Used for repeated/ sustained contractions (e.g. postural muscles) - fatigue resistant
Use aerobic/ slow oxidative respiration
Lots of mitochondria present

Question 2

What are the features of type 2a muscle fibres?

Answer 2

Used for intermediate contractions
Use aerobic and anaerobic respiration, fast oxidative respiration
Lots of mitochondria present

Question 3

What are the features of type 2b muscle fibres?

Answer 3

Fast twitch
Used for fast, powerful contraction (e.g. sprints) - rapidly fatigued
Use anaerobic respiration
Few mitochondria present

Question 4

What is a motor unit?

Answer 4

Motor neurone and the muscle fibres it innervates

Alpha motor neurones most common

Question 5

What is Myasthenia Gravis?

Answer 5

Condition where autoantibodies attack nicotinic ACh receptors on the post-synaptic membrane causing difficulties transmitting ACh across the NMJ
Symptoms: muscle weakness (esp. extraocular muscles, fascial muscles and bulbar muscles), fatigability

Question 6

What is the treatment for Myasthenia Gravis?

Answer 6

Acetylcholinesterase inhibitors (e.g. Neostigmine)

Question 7

What is Botulism?

Answer 7

Condition caused by Clostridium Botulinum which degrades the SNARE complex (protein complex that aids vesicle attachment to pre-synaptic membrane) causing a total block of the NMJ (as no ACh can be released)
Symptoms: Flaccid paralysis, paralysis of respiratory muscles

Question 8

What are T-tubules?

Answer 8

Invaginations of sarcolemma found in muscle fibres

Question 9

What is the function of Sarcoplasmic Reticulum?

Answer 9

Storage of calcium in muscle fibres

Question 10

What are myofilaments?

Answer 10

Proteins arranged in a highly organised way to enable contraction. 
Thick myofilaments (myosin) and thin myofilaments (actin) make up muscle fibres

Question 11

What is a sarcomere?

Answer 11

Functional unit of contraction

Region between 2 ‘Z lines’ (point where thin actin myofilaments anchor in muscle fibres)

Question 12

How do sarcomeres differ between resting and contraction?

Answer 12

Some degree of overlap between myosin and actin myofilaments at rest (to give muscle tone)
During contraction, thin actin myofilaments pull towards M line causing sarcomere to shorten (and thus the muscle to shorten as multiple sarcomeres work in unison)

Question 13

What are the features of myosin?

Answer 13

Head of myosin molecule contains an actin binding site and an ATPase site
Multiple myosin molecules form an A band with heads at different points to allow multiple cross-bridges to be formed with actin

Question 14

What are thin myofilaments comprised of?

Answer 14

3 proteins:
Actin (alpha-helical structure with myosin binding sites that are covered at rest by tropomyosin)
Tropomyosin (filamentous protein that runs along the groove of each twisted actin filament)
Troponin (protein complex made up of Troponin I, T and C)

Question 15

What are the functions of each protein in the Troponin protein complex?

Answer 15

Troponin C = binds to calcium
Troponin I = inhibits myosin binding site (when muscle is relaxed)
Troponin T = attaches to tropomyosin

Question 16

What is excitation-contraction coupling?

Answer 16

1. Depolarisation of muscle fibre membrane causing action potential to be propagated down T tubules
2. Causes conformational changes in dihydropyridine receptors (on T tubules) which leads to conformational changes in ryanodine receptors (on SR)
3. Causes calcium to be released from SR (thus increasing intracellular calcium concentration)
4. Calcium binds to Troponin C on thin myofilaments which leads to conformational change of tropomyosin thus exposing myosin binding site
5. Cross-bridges formed between actin molecules and myosin heads causing contraction

Question 17

What is the sliding filament theory?

Answer 17

Contraction caused by thick and thin myofilaments sliding over eachother

Question 18

How is a contraction terminated?

Answer 18

Troponin C releases calcium molecule in response to cessation of action potential firing
Tropomyosin returns to resting position blocking myosin-actin binding site
Calcium taken up into SR by Sarcoendoplasmic Reticulum Calcium ATPase

Question 19

What is Duchenne Muscular Dystrophy?

Answer 19

Absence of the Dystrophin protein that links the cytoskeleton with the extracellular matrix causing necrosis and destruction of muscle fibres and replaces them with adipose and connective tissue

Question 20

What are the clinical signs of DMD?

Answer 20

Peripheral muscle weakness
Gower’s Sign (bending over and climbing hands up legs to stand)
Psuedohypertrophy (esp.of calves)

Question 21

What is the general treatment for DMD?

Answer 21

Physiotherapy
Steroid treatment
MDT involvement to improve QoL

Question 22

What is Becker’s Muscular Dystrophy?

Answer 22

X-linked genetic disorder causing reduction in Dystrophin protein
Milder symptoms and slower progression than DMD

Question 23

What is polymyositis?

Answer 23

Autoimmune inflammatory disorder affecting skeletal muscle and causing muscle fibre necrosis
Features include proximal symmetrical muscle weakness and wasting; dysphagia; dysphonia; respiratory and cardiac muscle weakness (in severe cases)

Question 24

What is the treatment for polymyositis?

Answer 24

Steroids

Immunosuppressants

Question 25

What is dermatomyositis?

Answer 25

Polymyositis with skin changes 
Helitrope rash (purple discolouration and swelling around eyes) 
Gottron's papules (scaly rash on hands particularly around knuckles) 
Commonly associated with autoimmune disorders or a paraneoplastic syndrome

Question 26

What are the stages of cross-bridge cycling?

Answer 26

1. Calcium binds to Troponin C causing displacement of Tropomyosin (allowing myosin to bind to actin)
2. ATP binds to myosin head inducing conformational change and reducing affinity of myosin head for actin - myosin head releases actin
3. ATP hydrolysed to ADP and Pi by ATPase - release of energy changes myosin head to bent position causing a spring-like action in which myosin head can bind to actin at further point along
4. Phosphate released from myosin head causing myosin head to spring back to original position pushing the actin molecule further towards the M line - sliding motion shortens sarcomere (power stroke)
5. Action happening in multiple consecutive sarcomeres causing shortening of muscle fibre (contraction)