Muscle structures and pathologies Flashcards
What are the features of type 1 muscle fibres?
Slow twitch
Used for repeated/ sustained contractions (e.g. postural muscles) - fatigue resistant
Use aerobic/ slow oxidative respiration
Lots of mitochondria present
What are the features of type 2a muscle fibres?
Used for intermediate contractions
Use aerobic and anaerobic respiration, fast oxidative respiration
Lots of mitochondria present
What are the features of type 2b muscle fibres?
Fast twitch
Used for fast, powerful contraction (e.g. sprints) - rapidly fatigued
Use anaerobic respiration
Few mitochondria present
What is a motor unit?
Motor neurone and the muscle fibres it innervates
Alpha motor neurones most common
What is Myasthenia Gravis?
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
What is the treatment for Myasthenia Gravis?
Acetylcholinesterase inhibitors (e.g. Neostigmine)
What is Botulism?
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
What are T-tubules?
Invaginations of sarcolemma found in muscle fibres
What is the function of Sarcoplasmic Reticulum?
Storage of calcium in muscle fibres
What are myofilaments?
Proteins arranged in a highly organised way to enable contraction. Thick myofilaments (myosin) and thin myofilaments (actin) make up muscle fibres
What is a sarcomere?
Functional unit of contraction
Region between 2 ‘Z lines’ (point where thin actin myofilaments anchor in muscle fibres)
How do sarcomeres differ between resting and contraction?
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)
What are the features of myosin?
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
What are thin myofilaments comprised of?
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)
What are the functions of each protein in the Troponin protein complex?
Troponin C = binds to calcium
Troponin I = inhibits myosin binding site (when muscle is relaxed)
Troponin T = attaches to tropomyosin
What is excitation-contraction coupling?
- Depolarisation of muscle fibre membrane causing action potential to be propagated down T tubules
- Causes conformational changes in dihydropyridine receptors (on T tubules) which leads to conformational changes in ryanodine receptors (on SR)
- Causes calcium to be released from SR (thus increasing intracellular calcium concentration)
- Calcium binds to Troponin C on thin myofilaments which leads to conformational change of tropomyosin thus exposing myosin binding site
- Cross-bridges formed between actin molecules and myosin heads causing contraction
What is the sliding filament theory?
Contraction caused by thick and thin myofilaments sliding over eachother
How is a contraction terminated?
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
What is Duchenne Muscular Dystrophy?
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
What are the clinical signs of DMD?
Peripheral muscle weakness
Gower’s Sign (bending over and climbing hands up legs to stand)
Psuedohypertrophy (esp.of calves)
What is the general treatment for DMD?
Physiotherapy
Steroid treatment
MDT involvement to improve QoL
What is Becker’s Muscular Dystrophy?
X-linked genetic disorder causing reduction in Dystrophin protein
Milder symptoms and slower progression than DMD
What is polymyositis?
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)
What is the treatment for polymyositis?
Steroids
Immunosuppressants
What is dermatomyositis?
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
What are the stages of cross-bridge cycling?
- Calcium binds to Troponin C causing displacement of Tropomyosin (allowing myosin to bind to actin)
- ATP binds to myosin head inducing conformational change and reducing affinity of myosin head for actin - myosin head releases actin
- 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
- 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)
- Action happening in multiple consecutive sarcomeres causing shortening of muscle fibre (contraction)
