Lecture 5. Nicotinic Receptors of the Neuromuscular Junction & Autonomic Ganglia

Question 1

What competitively blocks reuptake of choline?

Answer 1

Hemicholinium 3

Question 2

What is reuptake of choline dependent on?

Answer 2

Na⁺

Question 3

What synthesises ACh from precursors choline and Acetyl Co-A from mitochondria?

Answer 3

Choline acetyltransferase (ChAT)

Question 4

What selectively inhibits ChAT?

Answer 4

Nothing, recent evidence suggests that it may be inhibited by amyloid proteins seen in Alzheimer’s disease

Question 5

What inhibits uptake and storage of ACh in synaptic vesicles?

Answer 5

Vesamicol

Question 6

What does tetrodotoxin (TTX) block?

Answer 6

Voltage-gated Na⁺ channels (no action potential - no release)

Question 7

What blocks P/Q & N-type voltage-gated Ca²⁺ channels?

Answer 7

Various toxins eg conatoxins (no Ca²⁺ influx - no release)

Question 8

What does botulinum toxin block?

Answer 8

Vesicle fusion - no release

Question 9

What do dendrotoxins block?

Answer 9

Voltage-gated K⁺ channels (more Ca²⁺ influx - more release)

Question 10

What does ziconotide act as?

Answer 10

A selective N-type voltage-gated calcium channel blocker

Question 11

How is ziconotide given and what is it used for?

Answer 11

Given via the intrathecal route for the management of severe pain

Question 12

What does synaptotagmin detect?

Answer 12

Increase in intracellular calcium

Question 13

What is black widow spider venom?

Answer 13

α-latrotoxin (α-LTX)

Question 14

What happens to the synapses when exposed to α-LTX?

Answer 14

Massive ACh release which causes muscle spasms

Question 15

What happens to the synapses after being exposed to α-LTX?

Answer 15

Depletion of vesicle pool
Desensitisation of neuromuscular junction
Inhibition of endocytosis
Distended terminal
Paralysis

Question 16

What is the effect of an α-LTX dimer?

Answer 16

Enhances calcium ion intake into the synapse

Question 17

What is the effect of an α-LTX tetramer?

Answer 17

Forms calcium ion channel in the synapse

Question 18

What does the release of each quanta of transmitter at a NMJ give rise to?

Answer 18

A miniature end plate potential (mEPP) via activation of nAChRs

Question 19

What do mEPPs summate to give?

Answer 19

An end plate potential (EPP), which, if large enough, can initiate an action potential and hence muscular contraction

Question 20

What terminates the activation of nicotinic ACh receptors at NMJ?

Answer 20

Acetylcholinesterase (AChE/AChase)

Question 21

What drugs inhibit AChE?

Answer 21

Anticholinesterases (eg nerve agents, neostigmine)
Increase the concentration and effects of ACh - can lead to muscle spasms

Question 22

What is tubocurarine?

Answer 22

Competitive non-depolarising blocker (antagonist)
Arrow poison - kills prey by respiratory paralysis

Question 23

What are the clinical side effects of tubocurarine?

Answer 23

Decreased BP due to ganglion block & resultant vasodilation

Question 24

What are the names of the two competitive non-depolarising blockers in clinical use?

Answer 24

Vecuronium & Rocuronium (few side effects)

Question 25

Is vecuronium or rocuronium rapid in onset?

Answer 25

Rocuronium

Question 26

What are all competitive non-depolarising blockers reversed by?

Answer 26

Anticholinesterases eg neostigmine

Question 27

What occurs in phase I block?

Answer 27

1. Persistent activation of endplate nicotinic - receptors by suxamethonium 2. Prolonged depolarisation of endplate 3. Inactivation of voltage-gated sodium channels

Question 28

What occurs in phase II block?

Answer 28

4. Desensitisation of endplate nicotinic receptors 5. Repolarisation of endplate 6. Receptor desensitisation maintains blockade

Question 29

What is suxamethonium?

Answer 29

Depolarising blocker (agonist) Used clinically Rapid onset of paralysis Short duration – broken down by plasmacholinesterases Tracheal intubation, electroconvulsive therapy

Question 30

What are the side effects of suxamethonium?

Answer 30

Bradycardia (decreased heart rate) due to M2 mAChR activation in heart K⁺ release in trauma (eg burns) – cardiac dysrhythmias & cardiac arrest Prolonged paralysis (2hr+) in 1:3500 people

Question 31

What do ganglion blockers do?

Answer 31

Reduce the actions of both the sympathetic and parasympathetic nervous systems

Question 32

At the neuromuscular junction, what does the activation of nicotinic receptors promote?

Answer 32

Skeletal muscle contraction and underpins physical movement and breathing

Question 33

What can drugs that block nicotinic neuromuscular transmission be used for?

Answer 33

Can be used in surgery to prevent unwanted muscular contractions, but by two different mechanisms

Question 34

What can drugs that block nicotinic receptors at the autonomic ganglia be used for?

Answer 34

Lowering blood pressure