Neuromuscular Junction Wk3

Question 1

Outline sequence of events of NMJ

Answer 1

• neurotransmitter release
• neurotransmitter role at muscle terminal
• neuromuscular receptor
• initiation of action potential
• fate of neurotransmitter
• initiation of contraction

Question 2

What is an NMJ?

Answer 2

• between a motor neuron and a muscle cell
• tuned for rapid reliable neurotransmission
• 1 neurone can only release 1 neurotransmitter

Question 3

What happens at the neuromuscular junction?

Answer 3

1. ITCHY: Impulse depolarises the pre-synaptic membrane
2. CHAINS: Calcium channels open and calcium ions diffuse into the presynaptic knob (motor end plate)
3. VANISH: Vesicles fuse with the membrane and release acetylcholine into the synaptic cleft
4. AFTER: Acetylcholine diffuses across the gap and binds to receptor proteins on the muscle cell membrane
5. DANGEROUS: the membrane becomes depolarised - the wave of depolarisation passes along the membrane and down the T tubules
6. SENTENCES: calcium ions are released from the sarcoplasmic reticulum
7. TARNISH: calcium ions cause tropomyosin to move away from the actin binding sites
8. MONKEYS: allowing myosin heads to bind

Question 4

What is Ca2+ sensor?

Answer 4

Synaptotagmin

Question 5

What does ACh do?

Answer 5

Binds to nicotinic ACh receptors on postsynaptic end-plate membrane (ionotropic/ligand-gated ion channel)

Question 6

What is the electrical effect of ionotropic receptor activation?

Answer 6

Small excitatory post synaptic potential (EPSP)

Question 7

Why is the NMJ a specialised synapse?

Answer 7

Pre-synaptic 
- multiple quanta release
Postsynaptic 
- Junctional folds
- high density of nACh receptors
- high density of voltage gated N’a+ channels

Question 8

What a massive sodium influx cause?

Answer 8

• Massive depolarisation

- End plate potential membrane potential hits -20 mV

Question 9

What does acetylcholine do as a transmitter at an end plate?

Answer 9

• ACh binds to nicotinic ACh receptors
• Channel opens - permeable to N’a+ and K+
• Em of muscle cell : -90mV
• Na+ influx is greater than K+ efflux ~ Ek
• EPP initiates an action potential in muscle (opening of N’a+ channels)
• EPP decays as it moves away from end-plate (nAChRs absent away from synapse)
• AP travels through muscle cell

Question 10

Summary of EPP properties

Answer 10

• Timing: pre-synaptic AP to EPP ~ 1 msec
• EPP generated by ligand-gated channels - opening voltage-gated channels
• EPP is very large (compared to most synaptic potentials): many ACh vesicles released & high density of nAChRs
• Threshold for AP generation easily passed (high density of voltage gated N’a+ channels at end plate)

Question 11

What does the postsynaptic action potential do?

Answer 11

• AP invades T tubule system

- Allolws transmission of AP deep into m,uncle fibre to separate myofibrils

Question 12

What happens to ACh?

Answer 12

• Hydrolysed by acetylcholinesterase (AChE)

Question 13

What is myesthenia gravis?

Answer 13

• affects 1: 200,000
• muscle weakness during sustained activity
• autoimmune disease of nAChR - reduced number of NMJ
• treatment is AChE inhibitors (prolongs signal, neostigme)