Synaptic Transmission and the Neuromuscular Junction

Question 1

List the staged of an AP passing to muscle

Answer 1

1. AP comes down axon to neuromuscular junction.
2. Ca2+ channels open, Ca2+ influx.
3. Ca2+ binds to synaptotagmin.
4. Vesicle brought close to membrane.
5. Snare complex make a fusion pore.
6. Transmitter ACh released through pore.
7. Ach binds nicotinic ACh receptor channels on muscle end-plate = conformational change.
8. channel opens, Na+ influx.
9. depolarisation, will also activate adjacent Na+ channels.
10. = muscle end-plate potential.
11. Ach esterase degrades Ach

Question 2

How can higher levels of neurotransmitter be released?

Answer 2

Size of AP cannot increase, however frequency can = increase Ca2+ conc = more transmitter released

Question 3

Describe Ca2+ voltage-gated channels

Answer 3

Very similar to Na+ channels. 4 subunits, Voltage sensing domain. L type = target of many drugs, can be blocked – stopped release of Ca – less response. Channels activate/inactivate slower then Na+ channels

Question 4

What are the 2 ways to block an nACh receptor?

Answer 4

Competitive blocker: binds, closing channel e.g. d-tubocurarine = paralysis

Depolarising blocker: binds closing then opening channel that is now desensitised to neurotransmitter e.g. succinylcholine (short-acting muscle relaxant and local anaesthetic)

Question 5

Give a clinical example where an action potential cannot occur

Answer 5

Myasthenia gravis –> autoimmune disease targeting nACh receptors = release of Ach is fine, but as the receptors are damaged, no Na+ K+ entry = no depolarisation = weakened end-plate potential

Question 6

What type of Ca2+ channel is important and why?

Answer 6

L type = target of many drugs, can be blocked – stopped release of Ca – less response

Question 7

What is a neuromuscular junction?

Answer 7

synapse between nerve and skeletal muscle fibre

Question 8

What enzyme breaks down ACh?

Answer 8

acetylcholine esterase

Question 9

What is the gap between the presynaptic nerve membrane and postsynaptic muscle membrane called?

Answer 9

synaptic cleft

Question 10

How can competitive blocking by d-tubocurarine be overcome?

Answer 10

increasing ACh conc

Question 11

Outline the difference between an Ca2+ and Na+ channel

Answer 11

Na+ in/active faster

Ca+ channels open at more +ve MP

Question 12

What does a muscle end-plate potential result in?

Answer 12

propagation of an AP along the muscle fibre

Question 13

What does depolarisation at the end of a neuron cause?

Answer 13

opening of Ca2+ voltage-gated ion channels = Ca2+ inward

Question 14

DHP (dihydropyrdines) block what type of Ca2+ channel?

Answer 14

L-type

Question 15

What is Ca2+ channel inactivation dependent on?

Answer 15

Ca2+ conc inside the cell

Question 16

What is the difference between a nicotinic and muscarinic AChR

Answer 16

nicotinic = ligand-gated

muscarinic = GCPRs

Question 17

When referring to an AP what is meant by all or nothing?

Answer 17

once threshold has been reached the AP will be fired and conducted along the whole length of the nerve or not at all

Question 18

What is an inactivated channel?

Answer 18

one that is open but ions cant travel through