Neuromuscular junction

Question 1

What is the neuromuscular junction?

Answer 1

Synapse between muscle fibre and motor neurone

Question 2

How does a signal reach the NMJ?

Answer 2

• It is a motor signal - nerve system sends information to muscles so they contract
• Signals come from motor cortex
• Reach muscle by going through neurons
• First neuron is upper motor neuron, axon leaves motor cortex and goes to medulla
• Travels through lateral corticospinal tract to reach synaptic contact with the lower motor neuron
• Lower motor neurone has axons reaching muscles
• 2 synaptic relays - one from brain to motor neuron and one from motor neuron to muscle fibers
• Motor neuron divides into branches (motor units) when it reaches the muscle

Question 3

What is a motor unit?

Answer 3

One motor neurone and all the muscle fibres it innervates

Question 4

How many muscle fibres does one motor unit supply?

Answer 4

Several

Question 5

How many neurones innervate each muscle fibre?

Answer 5

One - the muscle fibre only receives one signal

Question 6

How does the NMJ work?

Answer 6

• Signal comes from motor cortex through motor neuron and interacts with terminal
• Action potential transmitted to pre-synaptic membrane
• Opens voltage gated calcium channels
• Allows calcium to move into the cell
• Allows synaptic vesicles to fuse with pre-junctional membrane and release ACh into cleft
• Passively diffuses into cleft
• Binds to nAChR
• 2 molecules of ACh needed for conformational change
• Receptors open and allow ions to move through them according to concentration gradient - in this case sodium moves through, which creates mEPP
• mEPP not big enough to produce AP at post-junctional membrane
• Around 100 mEPPs needed for EPP
• Continues through muscle fibres
• Triggers release of calcium from SR to stimulate muscle contraction

Question 7

How is an electrical signal terminated?

Answer 7

• If the signal isn’t removed, the muscle continues to contract and ACh stays in cleft
• Acetylcholinesterase breaks down ACh into choline and acetate
• Reuse choline to synthesise more ACh
• Pre-junctional membrane takes up choline and makes more ACh in vesicles

Question 8

What do organophosphates do to the NMJ?

Answer 8

Normally, acetylcholinesterase catalyses the breakdown of ACh into acetate and choline. Organophosphates phosphorylate acetylcholine, reducing the ability of the enzyme to break it down. Concentration of ACh increases = cholinergic syndrome

Question 9

What is myasthenia gravis?

Answer 9

Antibodies block/destroy receptors for ACh at NMJ, preventing the muscle from contracting. Not enough nicotinic ACh receptors present means that mEPPs don’t accumulate to form an EPP for contraction

Question 10

What do neuromuscular blockers do to the NMJ?

Answer 10

Competitive antagonists that block transmission through the NMJ at nicotinic receptors by competing with ACh for the alpha sub units on the ACh receptors

Question 11

What does botulism toxin do to the NMJ?

Answer 11

Stops ACh being released at presynaptic membrane, which doesn’t allow muscles to contract and paralyses them, e.g. cardiac muscle in heart

Question 12

How many molecules of ACh are needed for conformational change?

Answer 12

2

Question 13

How many molecules of mEPP are needed for EPP?

Answer 13

Around 100

Question 14

What is ACh normally broken down into?

Answer 14

Acetate and choline

Question 15

Which enzyme breaks down ACh?

Answer 15

Acetylcholinesterase