Lecture 10

Question 1

What is the sequence of events at the NMJ?

Answer 1

1. action potential in axon
2. voltage gated Ca2+ channels open - Ca2+ influx
3. Ca2+ triggers vesicle fusion, Ach is released and diffuses in the cleft
4. Ach bind to nAchR on the muscle fiber
5. nAchR channel opens, Na+ enters the muscle fiber
6. local depolarisation spreads to extra-junctional membrane
7. depolarisation opens voltage-gated Na channels, muscle action potential triggered
8. action potential propagates along fiber
9. Ach is degraded by AchE

Question 2

Where are the Ca2+ channels located?

Answer 2

Near the vesicles, which allows coupling of Ca2+ transport into the cell with neurotransmitter exocytosis.

Question 3

What is the NMJ’s high safety mechanism?

Answer 3

This refer to the excess of Ach released onto the synaptic cleft. this is to ensure the trigger of an action potential.

Question 4

What are the structural characteristics of Nicotinic acetylcholine receptors (nAchR)?

Answer 4

they are ionotropic receptors. each receptor has 5 subunits, each with four transmembrane domains. subunits surround a pore in the membrane. this pore is created due to the receptor’s tertiary structure, is gated, and is normally closed. the sequence of amino acids in the pore determine what ions can pass through.

Question 5

What are the characteristics of the nAchR gate?

Answer 5

The receptor is chemically gated - ligand is Ach. the binding of Ach causes a conformational change, which opens the channel.
it has a non-selective cation channel, which is permeable to both Na+ and K+.
the Na+ influx into the cell causes depolarisation.

Question 6

What happens when the nAchR becomes desensitised ?

Answer 6

This occurs when the Ach is bonded for too long, and so the gate becomes desensitised. in order to reactivate it, the molecule must unbind first, for other Ach molecules to bind and activate it.

Question 7

What are Muscarinic Ach Receptors?

Answer 7

they are metabotrophic receptors which have indirect gating via a G-protein. the G-protein open a K+ channel, causing K+ efflux. these can be found in the CNS, ANS and smooth muscle.

Question 8

Pharmacology of nicotinic receptors

Answer 8

agonist: nicotine
antagonist: tubocurarine. blocks the receptors, resulting in paralysis.
also, alpha-neurotoxins (snake venom)

Question 9

Pharmacology of muscarinic receptors

Answer 9

agonist: muscarine. it disrupts and destructs the CNS and autonomic system.
antagonist: atropine

Question 10

What inhibits AchE?

Answer 10

1. endophonium

2. pyridostigmine

Question 11

What is Myasthenia Gravis?

Answer 11

It is an autoimmune disease of the NMJ. It reduces MNJ function and results in weakness, particularly of frequently used muscles.

Question 12

What causes Myasthenia Gravis?

Answer 12

antibodies degrade muscle nAchR, reducing the number of receptors and blocking the receptors.

Question 13

Why do MG symptoms come on with sustained contraction?

Answer 13

This is because the reduced number of receptors in the NMJ means that during sustained contraction, as there is a depletion of released Ach, depolarisation gets smaller and smaller and may not induce an action potential. there is transmission failure.

Question 14

Why do AchE blockers help in MG?

Answer 14

This is because AchE blockers delay the breakdown of Ach, so that Ach levels build up and transmission can occur.