ELM16: Muscle 1 Flashcards
What is the H zone in the sarcomere?
Thick filaments that don’t over lap
What is the A band in the sarcomere?
Entire length of thick filament
What is the I band in the sarcomere?
Thin filaments not overlapping thick
What is the optimum length of a sarcomere?
2.1-2.2
What is myosin?
Family of motor proteins
Head with ATPase activity
Motor powered by ATP hydrolysis
What is the structure of myosin?
2 heavy chains
2 essential light chains and 2 regulatory light chains
Heads that interact with actin
What is tropomyosin?
Runs along the actin chain
2 alpha helical proteins coiled together
1 per 7 actin monomers
What is troponin T?
Interacts with tropomyosin
What is troponin I?
inhibits the binding of myosin
What is troponin C?
Binds to calcium
What is the function of troponin?
Allows movement to be regulated by calcium
What is the process of the myosin actin complex causing contraction?
- Myosin binds ATP which dissociates bond between actin and myosin
- Myosin hydrolyses ATP and ADP and phosphate stay bound to head
- Head changes conformation to cocked state
- Weak bond forms between actin and myosin head at different position
- Phosphate dissociates and bond strengthens
- Head returns to resting which moves actin
- ADP dissociates and repeats
What is the role of troponin in regulating contraction?
- TnI binds to actin and blocks binding sites for myosin
- Contraction increases calcium concentration
- Calcium binds to TnC which changes conformation and uncovers binding sites
- Actin and myosin can now form
How does a T tubule interact with the sarcolemma?
T tubule associates with sarcolemma and makes a terminal cisterna
2 for each T tubule
What is the role of the T tubule?
Allows transmission of the action potential to inside sarcoplasmic reticulum
Signal translated to calcium
How is calcium concentration maintained inside the cell?
SERCA pump maintains high conc in sarcoplasmic reticulum and low conc in cytoplasm
What needs to happen to the concentration of calcium in the cytoplasm for contraction to be triggered?
Increase
How does the T tubule allow for concentration of calcium to increase in the cytoplasm?
- Action potential travels down T tubule
- DHP receptor changes the conformation
- Signal transmitted to ryanodine receptor through physical link
- Ryanodine receptor opens and calcium enters cytoplasm
What is the overall process of transmission from a nerve to muscle?
- Acetylcholine is released by a motor neuron
- nACh receptors activated
- Sarcolemma depolarised and action potential triggered and spread to T tubule
- DHP receptor activated and triggers ryanodine receptor
- Calcium ions released from sarcoplasmic reticulum
- Troponin C binds calcium and initiates contraction
- Calcium ions reenter sarcoplasmic reticulum
What is the structure of the NMJ in skeletal muscle?
A branch of motor neuron meets a muscle fibre and splits into lots of presynaptic nerve terminals
What is the end plate region?
The patch of muscle fibre membrane where presynaptic nerve terminals make contact
What are junctional folds?
Folds in the muscle fibre membrane under presynaptic terminals
What is myasthenia gravis?
Autoimmune disorder on skeletal muscle
Attacks nicotinic receptors and stops contraction
Causes weakness and fatigue
What is the overall pathological mechanism of myasthenia gravis?
Antibodies are against the receptor and bind to alpha subunits
What is the mechanism of MA where receptors become internalised?
- Cell recognises faulty receptor and removes from membrane through endocytosis
- Less receptors prevents contraction
What is the mechanism of MA where there is destruction and simplification of the end plate?
- Immune receptor recognises receptors and cells and attacks them
- Flattens the end plate to have wider synapse and less receptors
What is the mechanism of MG where the acetylcholine binding sites are blocked?
- Antibodies bind
- Act as antagonists and prevent acetylcholine from binding
How are MG patients diagnosed with muscle weakness patterns?
Face muscles affected first so can be observed
How are MG patients diagnosed with antibodies against nAChR?
Can test patients serum and see if antibodies are present
How are MG patients diagnosed with electromyography?
MG patients have decline in AP size
How are MG patients diagnosed with the tensilon/edrophonium test?
Patients given dose of acetylcholine inhibitor called edrophonium
If improvement it shows MG
How is MG treated with aceylcholinerase inhibitors?
Prevents breakdown of acetylcholine
How is MG treated with immunosuppressants?
Suppresses immune response and prevents breakdown of receptors
How is MG treated with plasma therapy?
Removes autoantibodies from circulation
What are nerve gases?
Irreversible inhibitors of AChE
Have compound sarin
What is sarin?
Absorbed through skin or lungs and deadly
What is the pathophysiology of sarin?
- Inhibits acetylcholinesterase at NMJ and cholinergic synapses
- Malfunction in every body system
- Causes death
What are the actions of sarin at the NMJ?
- An irreversible inhibitor of AChE
- Increases concentration of acetylcholine
- Muscle becomes limp as receptors enter desensitised state and can’t cause depolarisation
What is the molecular mechanism of sarin?
- Sarin binds to serine very strongly
- Enzyme can’t be recycled
- Acetylcholine can’t be broken down
What are two antidotes to sarin?
Muscarinic antagonist atropine
Pralidoxime to reactivate acetylcholinesterase
