The NMJ

Question 1

What is a neuromuscular junction?

Answer 1

A synapse between a motor neurone and a skeletal muscle fibre

Question 2

What signal does a NMJ propagate?

Answer 2

Action potential to muscle contraction

Question 3

How far do presynaptic motor axons terminate from the sarcolemma of a muscle fiber?

Answer 3

30nm

Question 4

How is the motor end plate modified to work as an NMJ?

Answer 4

Invaginations called post-junctional folds, which increase its surface area

Question 5

What lines the sarcolemma of the post synaptic membrane end plate?

Answer 5

Nicotinic acetylcholine receptors (nAChRs)

Question 6

What is the term used to describe the area where vesicles are grouped at the motor nerve terminal membrane?

Answer 6

Active zone

Question 7

How many vesicles are roughly clustered at the active zone?

Answer 7

~50

Question 8

What do vesicles in the motor nerve terminal contain?

Answer 8

ACh

Question 9

How are vesicles in the active zone kept close to the membrane?

Answer 9

Docked by proteins dystrophin and rapsyn.

Question 10

Where are the reserve pool of vesicles docked?

Answer 10

At the cytoskeleton further from the membrane

Question 11

What docks the reserve pool of vesicles?

Answer 11

Actin microfilaments

Question 12

What does the arrival of the action potential cause at the motor presynaptic terminal?

Answer 12

Opens voltage-dependent calcium channels and Ca2+ ions flow from the extracellular fluid into the presynaptic neuron’s cytosol.

Question 13

What is the effect of calcium influx into the presynaptic terminal?

Answer 13

Causes several hundred neurotransmitter-containing vesicles to fuse with the presynaptic neuron’s cell membrane through SNARE proteins to release their acetylcholine quanta by exocytosis.

Question 14

How do SNARE proteins lead to exocytosis?

Answer 14

The v-SNARES are associated with the vesicle membrane and the t-SNARES with the cell membrane these combine to form a cis-SNARE complex, also known as a “SNAREpin”.

Question 15

What is the term used to describe acetylcholine release in packets?

Answer 15

Quanta

Question 16

What does acetylcholine do after exocytosis?

Answer 16

ACh moves across synaptic cleft

The acetylcholine activates acetylcholine receptors, opening their ion channels which permits sodium ions to move into the endplate producing a depolarization

Question 17

Roughly how many nAChRs are bound to from one quanta?

Answer 17

~2000

Question 18

What is the depolarising effect of a single stimulation (single quanta)?

Answer 18

Depolarization of ~0.5 mV known as a miniature endplate potential (MEPP).

Question 19

What is the time interval between the arrival of the nerve impulse in the motor nerve terminals and the first response of the endplate?

Answer 19

0.5 -0.8 msec

Question 20

How many quanta are required to make an EPP?

Answer 20

~200

Question 21

How do quanta need to be released in order to produce an EPP?

Answer 21

Released simultaneously or in rapid series by a nerve impulse

Question 22

What is the EPP?

Answer 22

Chemically induced change in electric potential of the motor end plate.

Question 23

Does an EPP always produce an action potential propagation?

Answer 23

No

Question 24

How does an EPP lead to action potential propagation?

Answer 24

If the EPP depolarizes the cell to a crucial threshold level, it will fully activate sodium channels along the membrane and produce the action potential.

Question 25

What enzyme hydrolyses ACh bound to receptors?

Answer 25

Acetylcholinesterase

Question 26

How long does AChE take to act?

Answer 26

~0.16 ms

Question 27

Where is AChE bound?

Answer 27

Post synaptic membrane

Question 28

What happens to the liberated choline after breakdown?

Answer 28

Taken up again by the pre-synaptic neuron

Question 29

What does AChE break ACh into?

Answer 29

Choline and Acetic acid

Question 30

What happens to reabsorbed choline ?

Answer 30

ACh is synthesized by combining with acetyl-CoA through the action of choline acetyltransferase.

Question 31

What antagonises nAChr?

Answer 31

Tubocurarine, Veruconium

Question 32

What does tubocurarine do?

Answer 32

Antagonist of nicotinic ACh receptor

Question 33

What does veruconium do?

Answer 33

Antagonist of nicotinic ACh receptor

Question 34

When is veruconium used clinically?

Answer 34

Muscle-relaxing properties, which are used adjunctively to general anesthesia.

Question 35

What drug can reverse the effects of nAChr antagonists and why?

Answer 35

Neostigmine which inhibits AChE therefore more ACh is in the cleft and can compete for the receptors.

Question 36

What does suxamethonium do?

Answer 36

Depolarising drug, generates an action potential, AChE cannot remove the drug so the membrane cannot repolarise. The maintained depolarisation means that the voltage gated sodium channels are inactivatedm another AP cannot be propagated

Question 37

Why do your muscles relax when you take suxamethonium?

Answer 37

Muscle relaxation separate process to nerve stimulation

Question 38

What does botulinum toxin do?

Answer 38

Cleaves SNARE proteins meaning that the acetylcholine vesicles can’t bind to the intracellular cell membrane, preventing the cell from releasing vesicles of neurotransmitter.

Question 39

What are the effects of botulinum toxin and what is it clinically used for?

Answer 39

Stops nerve signaling, leading to paralysis of muscles.

Used to prevent excessive sweating, fine lines on skin

Question 40

What does neostigmine do?

Answer 40

Enhance cholinergic transmission by inhibiting AChE.

Question 41

When is neostigmine clinically useful?

Answer 41

Used to improve muscle tone in people with myasthenia gravis (autoimmune disorder against nAChr).

Question 42

On arrival of a single action potential, motor nerves release a number of quanta of transmitter approximately equal to..

Answer 42

100