Lecture 10 - Neuromuscular

Question 1

What structure passes a signal from a motor neurone to a muscle?

Answer 1

Neuromuscular junction

Question 2

What stimulates the release of neurotransmitter into the synaptic cleft of the neuromuscular junction?

Answer 2

Ca2+

Question 3

How does Ca2+ influx causing neurotransmitter release occur?

Answer 3

Depolarisation stimulates Voltage Gated Ca2+ Channels to open

Question 4

What generally happens at the nerve terminal once action potential reaches it?

Answer 4

VG Ca2+ channels open
Ca2+ influx
Increased [Ca2+]
ACh (Neurotransmitter) released into synaptic cleft

Question 5

How does an increased frequency in action potentials to a nerve terminal affect terminal Ca2+ influx and therefore neurotransmitter release?

Answer 5

Increased amount of Ca2+ influx
MORE Neurotransmitter released

Question 6

What is the structure of a Voltage-gated Ca2+ channel similar to?

Answer 6

Voltage gated Na+ channel

Question 7

What is the structure of a voltage gated Ca2+ channel?

Answer 7

1 alpha sub unit made up of 4 repeats
Charged amino acids on repeats I and IV

Question 8

What is a common Ca2+ channel?

Answer 8

L Type voltages gated Ca2+ channels

Question 9

What family of drugs are used to block L-Type Ca2+ channels?

Answer 9

DHP (Dihydropyridines)

E.g Nifedipine

Question 10

What is the significance of other subunits associating with Na+ channels or Ca2+ channels?

Answer 10

Fine tunes the properties
Ensures it carries out set function

Question 11

What can the post synaptic membrane of a neuromuscular junction be called?

Answer 11

End plate

Question 12

What receptors are present of the end plate/post synaptic membrane at a neuromuscular junction?

Answer 12

nACHR (Nicotinic Aceytlcholine receptors)

Question 13

Once Ca2+ influx to axon terminal at a neuromuscular junction has occured, what happens? How does the neurotransmitter get released into the cleft?

Answer 13

Ca2+ binds to synaptotagmin
Vesicle bought close to membrane
Snare complex make a fusion pore
Transmitter released through this pore

Question 14

Where is synaptotagmin?

Answer 14

On vesicle membrane

Question 15

Where is the snare complex?

Answer 15

On the presynaptic membrane

Question 16

How many ACh need to bind to the nACHR on the skeletal muscle membrane?

Answer 16

2 to each nAChR

Question 17

What is the selectivity of nicotinic Acetylcholine receptors like?

Answer 17

Not very specific
Allows cations to move through
Na+ and Ca2+ in
K+ out

Question 18

What type of channel are nAChR?

Answer 18

Ligand gated ion channels

Question 19

What happens when ACh binds to the AChR on the muscle membrane (end plate)?

Answer 19

Na+ influx into muscle causing depolarisation
If threshold potential reached Action potential in smooth muscle will be fired

Question 20

What is the depolarisation that occurs before an action potential occurs in the end plate (muscle) at a neuromuscular junction?

Answer 20

End plate potential

Question 21

How does amount of Ca2+ entry into axon terminal effect end plate potential?

Answer 21

Less Ca2+ in terminal = less neurotransmitter released = less nAChR opened = less Na+ into end plate = LOWER AMPLITUDE End plate potential

Question 22

What is the problem with lower amplitude end plate potentials at a neuromuscular junction?

Answer 22

Unlikely to depolarise enough to reach threshold potential for an action potential

Question 23

What is the enzyme that breaks down the ACh on the Na+ ligand gated ion channels (nAChR) on the end plate/postsynaptic membrane?

Answer 23

Aceytlcholine esterase
ACh esterase

Question 24

What is the effect of blocking nicotinic ACh receptors at neuromuscular junctions?

Answer 24

Paralysis since action potentials cannot be fired due to prevention of depolarisation (no Na+ influx)

Question 25

What are the 2 types of blockers of nACh receptors?

Answer 25

Competitive blockers Non competitive blockers

Question 26

What is an example of a competitive nAChR blocker?

Answer 26

d-tubocurarine (d-TC)

Question 27

What is the mode of action of d-TC (d-tubocurarine)?

Answer 27

Competes with ACh for the binding site of the nAChR (Ligand gated Na+ channel)

Question 28

What happens with the competitive blocker d-tubocurarine (d-TC) when ACh concentration is very high?

Answer 28

ACh may outcompete d-TC so its effects are minimal

Question 29

How does the nAChR blocker succinylcholine work?

Answer 29

Activates nAChR maintaining depolarisation causing the nACh channels to inactivate

Question 30

In surgery what is important to accompany a neuromuscular blocker and why?

Answer 30

Neuromuscular blocker = paralysis Anaesthetic = to not feel pain A patient who has only had a neuromuscular blocker wont be able to move but will be able to feel the pain

Question 31

What is Mayasthenia gravis?

Answer 31

Autoimmune disease targeting nACh receptors

Question 32

What effect does Mayasthenia gravis have on the end plate at a neuromuscular junction?

Answer 32

Damages the nAChR reducing number of functional channels More ACh needed to reach threshold potential

Question 33

What effect does Mayasthenia gravis have on muscles and why?

Answer 33

Profound weakness Due to endplate potentials being reduced in amplitude Means threshold potentials often not reached

Question 34

How can Myasthenia gravis be diagnosed?

Answer 34

Inhibit the ACh esterase enzyme so the ACh is not quickly broken down and can accumulate And then see if the muscle strength increases (more Ligand gated Na+ channels open so more likely that end plate potential reaches threshold)

Question 35

What is the test called to diagnose myasthenia gravis?

Answer 35

Edrophonium test Sees if facial muscle weakness improved by the ACh esterase inhibitor edrophonium chloride

Question 36

How is organophosphate poisoning bad?

Answer 36

Permanently inhibit ACh esterase

Question 37

Where are muscarinic Acetylcholine receptors located?

Answer 37

Following postganglionic parasympathetic neurones on the target tissues

Question 38

How does the type of synaptic transmission differ between nAChRs and mAChRs?

Answer 38

nAChR = fast synaptic transmission mAChR = slow synaptic transmission

Question 39

Why is nAChR fast synaptic transmission?

Answer 39

The receptor and ion channel are the same protein It is a ligand gated ion channel so depolarisation is fast

Question 40

Why is mAChR slow synaptic transmission?

Answer 40

mAChR is a G protein coupled receptor Receptor and ion channel are separate proteins G protein needs to be activated triggering a cascade of events in the cell leading to the opening of the ion channel