Skeletal Neuromuscular Junction

Question 1

How is ACh synthesised?

Answer 1

Synthesised from Choline & Acetyl coenzyme A (AcCoA) by the action of enzyme Choline Acetyl Transferase (CAT)

Question 2

What drug acts pre-junctionally to inhibit neuromuscular transmission?

Answer 2

Botulinum toxin - blocks process of exocytosis of ACh

Destroys key proteins involved

Used to treat:

• Blepharospasm - involuntary tight closure of the eyelids
• Hyperhidrosis - excessive sweating
• Bladder hyperactivity

Question 3

What forms a Nicotinic ACh receptor?

Answer 3

Formed from 5 protein subunits - (α, α, β, γ, δ) - formed around a non-selective cation channel

γ subunit in foetal muscle is replaced by an ε subunit in adult muscle

Question 4

How is the cation channel of the NaACh receptor opened?

Answer 4

It opens when 2 molecules of ACh bind to the protein complex - 1 to each α subunit

Question 5

What drug acts post-junctionally to inhibit neuromuscular transmission?

Answer 5

Reversible competitive antagonists act at the NACh receptor

They have affinity but 0 efficacy - prevent ACh binding and activating receptor

Clinical uses - muscle relaxant during surgery to allow lower doses of anaesthetics to be given

Effects can be reversed by drug Neostigmine

Question 6

What is Suxamethonium and how does it work?

Answer 6

Depolarising muscle relaxant

Rapid onset of action - within 60 seconds

Agonist at NACh receptor

Has affinity and efficacy - binds to receptor and activates

Suxamethonium is not broken down by AChE - thus prolonged depolarisation

Thus Na channels get trapped in inactivated state - leading to muscle relaxation

Broken down by enzyme Butyrylcholinestrase

Question 7

What are Anticholinesterase drugs and give examples

Answer 7

Prevent breakdown of ACh - thus increasing conc of ACh at neuromuscular juntion

Neostigmine
Edrophonium

Question 8

What is Myasthenia Gravis (MG)?

Answer 8

Auto-immune disease => Neuromuscular weakness

Antibodies bind to α-subunits of NAChR leading to their destruction

Question 9

How is MG diagnosed and treated?

Answer 9

Edrophonium - short duration of action - thus used to diagnose MG

Neostigmine - lasts for 4 hours - thus used in treatment

Increased conc of ACh enhances neuromuscular transmission - thus increasing the likelyhood of ACh activating NAChR’s