Synaptic Transmission And Neuromuscular Junction (session 5)

Question 1

How is a signal passed from nerve to muscle?

Answer 1

Neuromuscular junction (synapse between nerve and skeletal muscle fibre)

Question 2

Which voltage-gated channels are present in the nerve terminal?

Answer 2

Na+
K+
Ca2+

Question 3

What happens at the nerve terminal? (4)

Answer 3

1. Depolarisation
2. Opens voltage-gated Ca2+ channels
3. Ca2+ entry
4. Release of neurotransmitter

Question 4

Why can the internal concentration of Ca2+ be increased significantly at the nerve terminal?

Answer 4

Because the concentration of Ca2+ inside is so low

Question 5

Complete the sentence:

Increasing the frequency of AP _________ the amount of nerve terminal Ca2+ entry

Answer 5

Increases

Question 6

The alpha subunit of voltage-gated Ca2+ channels is very similar to which other voltage-gated channel?

Answer 6

Na+

Question 7

What is a pore forming subunit necessary for?

Answer 7

A functional channel

Question 8

What do other associated subunits do in channels?

Answer 8

Fine-tune the properties and enable correct regulation of channel activity

Question 9

True or false: voltage-gated Ca2+ channels activate quicker than voltage-gated Na+ channels

Answer 9

FALSE

Question 10

What does acetylcholine esterase do?

Answer 10

Breaks down ACh

Question 11

What type of acetylcholine receptors are on the postsynaptic membrane?

Answer 11

Nicotinic

Question 12

Describe the process of transmitter release (5)

Answer 12

1. Ca2+ entry through Ca2+ channels
2. Ca2+ binds to synaptotagmin
3. Vesicle brought close to membrane
4. Snare complex make fusion pore
5. Transmitter released through this pore

Question 13

What is reverse potential?

Answer 13

No net flow of charge when the channel is open-halfway between K+ and Na+ equilibrium potential

Question 14

What happens at the synaptic cleft when two ACh molecules bind to the receptor?

Answer 14

Leads to a conformational change and the pore opens

Question 15

What is excitation contraction coupling?

Answer 15

Muscle AP initiated adjacent to the end-plate and propagates along the muscle fibre.
The AP initiates contraction of the skeletal muscle fibre.

Question 16

Give an example of a competitive nicotinic ACh receptor blocker

Answer 16

Tubocurarine

Question 17

Give an example of a depolarising nicotinic ACh receptor blocker

Answer 17

Succinylcholine

Question 18

How can the block by d-tubocurarine be overcome?

Answer 18

By increasing the concentration of ACh

Question 19

What is a potential problem of using succinylcholine during operations?

Answer 19

Sometimes the anaesthetic doesn’t work but the neuromuscular blocker does work so the patient is left paralysed but can still feel pain

Question 20

Name an autoimmune disease targeting nACh receptors

Answer 20

Myasthenia gravis

Question 21

What happens in myasthenia gravis?

Answer 21

Patients suffer profound weakness

Weakness increases with exercise

Question 22

What causes myasthenia gravis?

Answer 22

Antibodies directed against nACh receptor on postsynaptic membrane of skeletal muscle. Antibodies lead to loss of functional nAChR by complement mediated lysis and receptor degradation. Endplate potentials are reduced in amplitude, leading to muscle weakness and fatigue

Question 23

Complete the sentence:

ACh binds to _________ ACh receptors on the muscle end-plate , causing a depolarisation called the ___-_____ _________

Answer 23

Nicotinic

End-plate potential

Question 24

Why does the muscle fibre contract when an AP is initiated there?

Answer 24

Due to excitation-contraction coupling

Question 25

What is the difference between nicotinic and muscarinic receptors?

Answer 25

Nicotinic receptors are ligand-gated | Muscarinic receptors are in the parasympathetic nervous system so there is no intrinsic ion channel involved

Question 26

Why do muscarinic AChR produce a slower response than nicotinic AChR?

Answer 26

mAChR are coupled to G-proteins which trigger a cascade of events in the cell