S5 - Neuromuscular Junctions

Question 1

How does an action potential open Ca2+ channels?

Answer 1

1. Depolarisation/AP at the nerve terminal
2. Voltage-gated Ca2+ channels to open
3. Ca2+ influx

Question 2

Do Ca2+ or Na+ channels inactivate slower?

And which needs more depolarisation to open?

Answer 2

Ca2+

Ca2+

Question 3

What leads to inactivation of Ca2+ channels?

Answer 3

Increased Ca2+ concentration inside cell

Question 4

What is the diversity of Ca2+ channels?

Answer 4

There are different isoforms which have different blockers and locations within the body.

Question 5

What is fast synaptic transmission?

Answer 5

ACh binding to receptor results in opening of the Na+ channel (fast and local response)

Question 6

What is the difference between response produced between nicotinic and muscarinic ACh receptors?

Answer 6

Nicotinic - fast synaptic transmission, ligand-gated (fast and local)

Muscarinic - slower synaptic transmission, GPCR (slow and throughout the cell as involves a signalling molecule and a cascade to open Na+ channel)

Question 7

What are the two types of neuromuscular blockers?

Answer 7

1. Competitive blockers

2. Depolarising blockers

Question 8

What do competitive blockers do at the neuromuscular junction?

Answer 8

Bind to the receptor site of ACh preventing ACh from binding (can be overcome by increasing ACh concentration). Prevents channels opening so prevents depolarisation,.

Question 9

What is an example of a competitive blocker at a neuromuscular junction?

Answer 9

d-tubocurarine (used to be an anaesthetic)

Question 10

What do depolarising blockers do at the neuromuscular junction?

Answer 10

A competitive inhibitor of ACh. Binds to ACh receptor site and activates the receptor and leads to continuous depolarisation (as not broken down by ACh-esterase). Eventually leads too inactivation of Na+ channels, so no action potential occurs.

Question 11

What is an example of a depolarising block at a neuromuscular junction?

Answer 11

Succinylcholine

Question 12

How is myasthenia gravis treated?

Answer 12

With acetylcholinesterase inhibitors e.g pyridostigmine.

Used to stop ACh breakdown, so more ACh available to help with muscle stimulation.

Question 13

What is myasthenia gravis?

Answer 13

An autoimmune disease on which autoantibodies target and destroy nicotinic ACh receptors - makes it harder for an action potential to be generated (harder to reach threshold). Causes muscle fatigue/weakness.

Question 14

How does a Ca2+ influx result in neurotransmitter release?

Answer 14

1. Influx of Ca2+
2. Ca2+ binds to synaptotagmin
3. Vesicle migrates to membrane
4. Snare complex makes a fusion pore
5. Release of NT from vesicles by exocytosis through the fusion pore