ND3: Synaptic release

Question 1

How is a signal passed from nerve to muscle?

Answer 1

The action potential is initiated at the axon hillock

The local circuit theory causes the movement of signal from nerve to muscle with no loss of amplitude

Question 2

What is the neuromuscular junction?

Answer 2

The synapse between a nerve and a skeletal muscle fibre

Question 3

What type of synapse is a neuromuscular junction? Why?

Answer 3

Chemical synapse

Involves the release of a chemical, e.g. acetylcholine

Question 4

Why are there lots of voltage-gated Ca²⁺​ ion channels at the presynaptic membrane?

Answer 4

They are crucial for transmitter release

Question 5

What effect does depolarisation have on Ca²⁺ channels?

Answer 5

It opens them

Question 6

What happens when voltage-gated Ca²⁺ ion channels are activated?

Answer 6

The release of transmitter from nerve terminal is initiated

Question 7

What are vesicles?

Answer 7

Small membrane-bound spheres containing large concentrations of acetylcholine

Question 8

What happens at the nerve terminal?

Answer 8

1. The voltage-gated Ca²⁺ ion channels are closed at the resting potential
2. Action potential arrival opens the voltage-gated Ca²⁺ ion channels
3. Ca²⁺ enters and triggers the release of transmitter

Question 9

How can the Ca²⁺ influx through ion channels cuase such a large increase in [Ca²⁺]_i?

Answer 9

The concentration of Ca²⁺ inside is so low, so even a small increase in ions will raise the concentration significantly

Question 10

Why does the Ca²⁺ concentration need to be so tightly controlled?

Answer 10

Involved in muscle contraction, release of hormones, and release of transmitter

Question 11

How can more neurotransmitter be released?

Answer 11

By having multiple action potentials in quick succession, which will cause a huge influx of Ca²⁺ and therefore lots of release of transmitter

Question 12

Why are multiple action potentials required to release more transmitter?

Answer 12

Because action potentials are only one size so there cannot be ‘bigger action potentials’

Question 13

With respect to K⁺ and Na⁺ channels, how quickly do Ca²⁺ channels activate and inactivate?

Answer 13

More quickly than K⁺ channels but more slowly than Na⁺ channels

Question 14

Why can Ba²⁺ be used as a model for Ca²⁺ channels?

Answer 14

It will pass through the pore of Ca²⁺ channels

Question 15

Compare the inactivation of Ca²⁺ channels when Ca²⁺ and Ba²⁺ flow through the channel. What does this suggest?

Answer 15

When Ba²⁺ flows through the channels, much less inactivation is seen

This suggests that increased intracellular Ca²⁺ concentration leads to inactivation of Ca²⁺ channels

Question 16

What are motor end plates?

Answer 16

The sites where muscle mibres make contact with axons

Question 17

For what are motor end plates responsible?

Answer 17

Transmitting the signal from the nerve to the muscle

Question 18

What is the role of mitochondria at the neuromuscular junction?

Answer 18

Take up Ca²⁺, otherwise transmitter would be released at all times

Question 19

What is the role of Schwann cells?

Answer 19

Provides the cell with its myelin sheath

Question 20

What is the role of acetylcholinesterase?

Answer 20

Breaks down acetylcholine very quickly to make sure it doesn’t activate the receptor for too long

Question 21

What is the role of acetylcholine receptors on the postsynaptic muscle membrane?

Answer 21

Acetylcholine binds to them to carry on the signal from the nerve to the muscle

Question 22

What is the process of transmitter release?

Answer 22

1. Ca²⁺ entry through voltage-gated Ca²⁺ channels
   
   • Significant increase due to low Ca²⁺ concentrations
2. Ca²⁺ binds to synaptotagmin
   
   • Brings vesicles closer to the nerve membrane
3. Snare complex makes a fusion pore
   
   • Forms a pathway between the vesicle and the synaptic cleft
4. Transmitter released through this pore

Question 23

To what receptors does acetylcholine bind?

Answer 23

Nicotinic acetylcholine receptors (nAChR)

Question 24

What type of channel is nAChR?

Answer 24

A ligand-gated cation-specific ion channel

Question 25

How is the skeletal muscle depolarised?

Answer 25

1. ACh diffuses across the synaptic cleft thus increasing the concentration of ACh
2. Two molecules of ACh bind to nAChR causing a conformational change
3. The pore of nAChR opens and allows Na⁺ in and K⁺ out at equal rates
4. Na⁺ influx predominates over K⁺ efflux because the resting potential is much closer to E_K than E_Na
5. This causes depolarisation

Question 26

How does the structure of the nicotinic receptor affect the depolarisation of skeletal muscle?

Answer 26

• The nicotinic receptor has five subunits (2α, 1β, 1γ, 1δ)
• Each α subunit has a binding site for ACh (hence the need for two ACh molecules)
• The binding of ACh causes the diameter of the pore to increase, so ions can flow through and depolarise the endplate of the muscle

Question 27

What happens to the endplate potential if the external Ca²⁺ concentration is decreased?

Answer 27

The endplate potential will decrease because the transmitter release is dependent on Ca²⁺ entry

Question 28

How does d-tubocurarine (d-TC) act as a competitive block?

Answer 28

It fits into the binding sites of the nAChR, preventing ACh from binding

Threshold is not reached, therefore there will be no action potential generated, therefore paralysis occurs

Question 29

How can the competitive block caused by d-tubocurarine (d-TC) be overcome?

Answer 29

By increasing the concentration of ACh which increases the chance of ACh finding available binding sites

Question 30

What are the two types of neuromuscular block? Give an example of each.

Answer 30

Competitive block, e.g. d-tubocurarine (d-TC)

Depolarising block, e.g. succinylcholine

Question 31

How does succinylcholine act as a neuromuscular block?

Answer 31

• When succinylcholine is released, the nAChRs will still be activated, but ACh will not be broken down by AChE
• This results in a prolonged depolarisation at the neuromuscular junction resulting in continuous activation of the Na⁺ channels
• Adjacent Na⁺ channels will become inactivated so the depolarisation is maintained and no action potential will be generated