Skeletal Neuromuscular Junction

  • Created by: LBCW0502
  • Created on: 03-10-18 15:52
Which neurotransmitter is involved in the somatic efferent system?
ACh
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Which type of receptor is involved in the somatic efferent system?
Nicotinic AChR
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What is the effector in the somatic efferent system?
Skeletal muscle
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What are the three types of muscle?
Smooth, cardiac and skeletal (striated)
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What is the skeletal NMJ?
Skeletal muscle joined to myelinated motor nerve
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How does the presence of myelin affect action potentials?
Myelinated nerves allow action potentials to be conducted rapidly
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Describe the structure of the skeletal neuromuscular junction (motor unit)
Single synapse between nerve and skeletal muscle (focally innervated). Single nerve (branching, controls activity of multiple muscle fibres)
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How does the number of neurones in areas e.g. leg differ from that of other areas e.g. fingers?
In large skeletal muscles, fine control is not needed so a single nerve regulates activity of hundreds of muscle fibres. In small skeletal muscles, motor nerve innervates 5-10 muscle fibres
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Describe features of the neuromuscular junction
Nerve ending sits in an indentation on the surface of muscle fibre (junctional cleft). Schwann cells (form myelin sheath) sit on neuron (sealed off, difficult to get drugs past Schwann cell and into nerve). SA of muscle increased (folded) - endplate
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How large is the gap between the nerve and muscle?
60 nm - chemical synaptic transmission occurs
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Which neuroreceptor is found in the membrane of skeletal muscle?
Nicotinic AChR (exception - damaged nerve, nicotinic AChR appears all over the muscle)
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Drugs can modify synaptic transmission by acting on which processes?
Presynaptically/pre-junctionally - synthesis, storage, release (of neurotransmitter). Post-synaptically - receptors, removal mechanism (of neurotransmitter)
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Outline the key steps in cholinergic neurotransmission (6)
Action potential in presynaptic neurone. Depolarisation of nerve terminal. Opening of voltage-gated Ca 2+ channels. Ca 2+ entry into nerve terminal. Release of acetylcholine by exocytosis. Activation of postsynaptic receptor
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Describe the pre-junctional events in cholinergic neurotransmission
ACh is synthesised from choline and AcCOA using Choline Acetyl Transferase (CAT - transfer of acetyl group). Choline taken up into nerve terminal from extracellular space by transporter
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How can drugs act pre-junctionally to inhibit cholinergic transmission?
Synthesis - hemicholinium used to block choline transporter to prevent uptake of choline (no clinical use). Storage - vesamicol used to block packaging. Release - Mg 2+ ions or botulinum toxin used to block Ca2+ channels, prevent exocytosis
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Why does hemicholinium and vesamicol have no clinical use?
Either way there is still a significant amount of ACh in the nerve terminal for neurotransmission to occur (takes a long time to have an effect)
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Describe features of Botulinium toxin
Extremely potent, lethal dose in mic is 1 picogram. Death occurs due to paralysis of respiratory muscles. Destroys SNAP-25 (involved in exocytosis). Used to treat blepharospasm, hyperhidrosis, bladder hyperactivity, headache, MS, cerebral palsy
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Describe the post-junctional events in neuromuscular transmission
ACh diffuses across junctional gap and activates nicotinic AChR on muscle membrane. AChE breaks down ACh (found in gap). Action potential in nerve leads to release of 'puff' of ACh rapidly removed by AChE
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Describe features of NAChR
Activated by nicotine (agonist). Formed from 5 protein sub units (2 alphas, beta, gamma, epsilon) surrounding ion channel. 2 ACh molecules bind to alpha units. Opening of channel leads to depolarisation of end-plate region of muscle membrane
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What is the end plate potential (epp)?
The depolarisation of the muscle membrane produced following activation of NAChR - a form of excitatory postsynaptic potential (EPSP)
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Describe features of the end plate potential (epp)?
Role is to depolarise muscle membrane potential to -55 mV. Voltage gated Na channels open, rapid all or nothing depolarisation of action potential. Propagation from endplate and depolarisation across muscle surface
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Describe features of drugs which post-junctionally inhibit neuromuscular transmission
Reversible competitive antagonists at nicotinic AChR. Non-depolarising muscle relaxants. Have affinity but no efficacy, so bind to receptor but doesn't open associated ion channel. Prevent ACh binding/activating receptor
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Give examples of drugs which act post-junctionally to inhibit neuromuscular transmission
Tubocurarine (poison darts). Vecuronium. Atracurium and Pancuronium
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Describe the clinical uses of reversible competitive antagonists
Used as muscle relaxants during surgery to allow lower doses of general anaesthetics to be administered. Effects last for 15-40 minutes depending on drug. Patient artificially ventilated. Effects can be reversed by neostigmine
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Describe features of suxamethonium as a depolarising muscle relaxant
Succinylcholine. Acts as an agonist at NAChR (both affinity and efficacy, binds to receptor, activates it, opens ion channel, depolarisation of muscle membrane). Suxamethonium is not broken down by AChE so it lingers - prolonged depolarisation
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Describe features of the complex mechanism of action (1)
On membrane depolarisation, channels open before closing into an inactivated state. Once inactivated, cannot re-open unless back in resting state (membrane potential needs to be back to resting value). ACh short lived
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Describe features of the complex mechanism of action (2)
Repolarisation (recover from inactivation). Suxamethonium - depolarisation is prolonged, Na channels get trapped in inactivated state and cannot support another action potential
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Why is suxamethonium used as a muscle relaxant?
Short-duration for ECT/intubation, broken down by BChE (enzyme in blood plasma). After IV injection, effects last for a few minutes (exception for patients with genetic deficiency for BChE- long effect) - cause muscle contraction- pain post-operation
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Describe features of AChE drugs
Inhibited by drugs e.g. neostigmine and edrophonium. Drugs prevent breakdown of ACh (increase concentration at NMJ). Neostigmine reverse effects of reversible competitive antagonists but not depolarising muscle relaxant suxamethonium
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Describe features of myasthenia gravis
Auto-immune disease characterised by neuromuscular weakness. Antibodies bind to alpha units, cross link adjacent NAChR. Edrophonium has short duration (5 mins, diagnosis) Neostigmine lasts 4 hours (treatment). Increase ACh enhances neurotransmission
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Card 3

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What is the effector in the somatic efferent system?

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Card 4

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What are the three types of muscle?

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Card 5

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What is the skeletal NMJ?

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