Lecture 1, 2 & 3 - Physiology and Pharmacology of the Neuromuscular Junction

Question 1

What allows for communication at the synapse

Answer 1

The release of chemical messengers (neurotransmitters)

Question 2

Where are neurotransmitters released from to allow communication at the synapse

Answer 2

The presynaptic nerve terminals

Question 3

What do neurotransmitter act upon on the post synaptic membrane

Answer 3

Receptors

Question 4

What are the five steps involved in the release of neurotransmitters

Answer 4

Synthesis, storage, release, activation and inactivation

Question 5

What can affect the steps involved with the release of neurotransmitters

Answer 5

Drugs and toxins

Question 6

Why are neurotransmitters stored

Answer 6

For protection and so that the quantity of neurotransmitter released can be controlled

Question 7

How can drug enhance synaptic transmission

Answer 7

By direct stimulation of postsynaptic receptors or by indirect action

Question 8

What are examples of direct stimulation of synaptic transmission

Answer 8

Natural transmitters and analogues

Question 9

What indirect action causes enhanced synaptic transmission

Answer 9

Increasing transmitter release and the inhibition of transmitter removal

Question 10

How can drugs inhibit synaptic transmission

Answer 10

By blocking synthesis, storage or release of neurotransmitter from the presynaptic neurone and by also blocking post synaptic receptors

Question 11

What are the two different types of drugs that act directly on receptors

Answer 11

Agonist and antagonists

Question 12

What are agonists

Answer 12

Drugs, hormones or transmitters that bind to specific receptors and initiate a conformational change

Question 13

Two important properties of agonists

Answer 13

Affinity and efficacy

Question 14

What is the affinity of an agonist

Answer 14

The ability of the agonist to bind to the receptor

Question 15

What is the efficacy of an agonist

Answer 15

The ability of an agonist, once bound to a receptor, to initiate a biological response

Question 16

Since agonists bind and activate receptors they have both

Answer 16

Affinity and efficacy

Question 17

Role of antagonists

Answer 17

They bind to receptors but do not activate them

Question 18

Do antagonists have affinity and efficacy

Answer 18

The have affinity but lack efficacy

Question 19

What is a competitive antagonist

Answer 19

It competes with the agonist for the agonist binding site on the receptor

Question 20

How is a block by an antagonist reversed

Answer 20

By increasing the agonist concentration

Question 21

How are synapses classified

Answer 21

By the neurotransmitter released from the presynaptic neurone

Question 22

What is the classification of synapses where the presynaptic neurone is acetylcholine

Answer 22

Cholinergic

Question 23

What are the receptors upon which ACh acts on known as

Answer 23

Cholinoceptors

Question 24

What are the two classes of cholinoceptors

Answer 24

Nicotinic ACh receptors and muscarinic cholinoceptors

Question 25

What activates nicotinic ACh receptors

Answer 25

ACh or nicotine

Question 26

What activates muscarinic receptors

Answer 26

ACh or muscarine

Question 27

What type of receptor is the nicotinic ACh receptor

Answer 27

Transmitter-gated ion channel

Question 28

How do nicotinic ACh receptors operate

Answer 28

An agonist binds to the receptor which induces a rapid conformational change to open the channel. The channel is selective for certain ions and the signalling happens extremely fast.

Question 29

What are the nicotinic ACh receptors composed of

Answer 29

Separate protein subunits

Question 30

What do the separate protein subunits of a nicotinic ACh receptor form

Answer 30

A central ion conducting channel

Question 31

What do the separate protein subunits in a nicotinic ACh receptor allow for

Answer 31

Rapid changes in the permeability of the membrane to certain ions and rapidly alter membrane potential

Question 32

Once the nicotinic ACh receptors are activated what does this also cause the activation of

Answer 32

The associated nicotinic cation channels

Question 33

Once the nicotinic cation channels open what moves into the muscle fibre

Answer 33

Na+ ions

Question 34

What does an influx of Na+ ions cause in the muscle fibre

Answer 34

Local depolarisation at the endplate region

Question 35

What does motor nerve stimulation cause

Answer 35

The synchronous release of many vesicles, which causes the summation of MEPPs which go on to produce an EPP

Question 36

What does the EPP cause

Answer 36

It depolarises the membrane potential to threshold

Question 37

When the membrane potential is at threshold what is activated

Answer 37

Voltage-gated Na+ channels and this induces an action potential

Question 38

How to calculate the quantal content

Answer 38

The mean EPP amplitude (mV) ÷ the mean MEPP amplitude (mV)

Question 39

Do MEPPs or EPPS occur spontaneously

Answer 39

MEPPs

Question 40

What is required to cause an EPP to occur

Answer 40

Motor nerve stimulation

Question 41

What synthesises ACh from Acetyl Co-A and choline

Answer 41

Choline acetyl transferase (CAT)

Question 42

Within the synapse where does the Acetyl Co-A come from

Answer 42

The mitochondria

Question 43

What step is Na+ dependent

Answer 43

Reuptake of choline

Question 44

What is the reuptake of choline blocked by

Answer 44

Hemicholinum 3

Question 45

What blocks the transport of ACh into vesicles

Answer 45

The inhibition of the ACh transporter

Question 46

What inhibits the ACh transporter

Answer 46

Vesamicol

Question 47

What is the action of tertrodoxin (TTX)

Answer 47

It blocks the Na+ channels so no action potential can be generated

Question 48

What blocks voltage-gated Ca2+ channels

Answer 48

Conotoxins

Question 49

When voltage-gated Ca2+ channels are blocked what happens to the quantal content

Answer 49

The EPP amplitude decreases but there is no change in the MEPP amplitude so the quantal content decreases

Question 50

What is the action of dendrotoxin

Answer 50

It blocks the voltage-gated K+ channel

Question 51

What does the blockage of voltage-gated K+ channels cause

Answer 51

A prolonged action potential

Question 52

How does dendrotoxin affect the quantal content

Answer 52

The EEP amplitude is increased but there is no change in the MEPP amplitude so the quantal content increases

Question 53

What does botulinum toxin do

Answer 53

It blocks vesicle fusion so there is no release

Question 54

How does botulinum toxin affect the quantal content

Answer 54

The EPP amplitude decreases and the MEPP amplitude remains the same so the quantal content decreases

Question 55

What effect does turbocaranine have on muscles

Answer 55

It is a muscle relaxant

Question 56

What is turbocaranine

Answer 56

A competitive non-depolarising neuromuscular blocking agent

Question 57

What is turbocaranine reversed by

Answer 57

Anticholinesterases

Question 58

What is alpha-bungarotoxin

Answer 58

An irreversible antagonist

Question 59

What is suxamethonium

Answer 59

A muscle relaxant with rapid onset and a short duration

Question 60

What is suxamethonium metabolised by

Answer 60

PLASMA ( i.e. butyric cholinesterase)

Question 61

What is involved in the phase one block of suxamethonium

Answer 61

Persistant activation of endplate nicotinic receptors, prolonged depolarisation of the endplate and the inactivation of voltage-gated sodium channels

Question 62

What is involved in the phase two block of suxamethonium

Answer 62

Desensitisation of endplate nicotinic receptor and depolarisation of endplate. The receptor desensitisation maintains the blockade.

Question 63

Is suxamethonium an agonist or antagonist

Answer 63

Agonist

Question 64

Where are true acetylcholinesterase found

Answer 64

At the cholinergic synapse, bound to the postsynaptic membrane

Question 65

Where are pseudo-cholinesterases found

Answer 65

In plasma

Question 66

What are pseudo-cholinesterases important in

Answer 66

Inactivating the depolarising neuromuscular blocker, suxamethonium

Question 67

What inhibits both true and pseudo-cholinesterases

Answer 67

Anticholinesterases

Question 68

What is neostigmine

Answer 68

An anticholinesterase

Question 69

What action does neostigmine have on the quantal content

Answer 69

It increases both the amplitude of both the EPP and MEPP so there is no effect on the quantal content

Question 70

What is the function of neostigmine

Answer 70

It prolongs the duration of the MEPP and EPP due to the increased life-time of ACh in the synaptic cleft

Question 71

What do anticholinesterases do

Answer 71

The inhibit the breakdown of ACh by inhibiting acylecholinesterase

Question 72

What are some clinical uses of anticholinesterase drugs

Answer 72

Reversal of neuromuscular paralysis, diagnosis and treatment of myasthenia graves and the treatment of Alzheimer's disease

Question 73

How is recovery from anticholinesterases achieved

Answer 73

A new enzyme has to be synthesised

Question 74

What are dyflos

Answer 74

Volatile, non-polar, lipid-soluble molecules

Question 75

What can reverse nerve gas

Answer 75

By atropine and oximes

Question 76

What does atropine do

Answer 76

It counteracts the effects of excessive muscarinic receptor stimulation by ACh

Question 77

What function do oximes have

Answer 77

To reactivate the AChase