Neuromuscular Junction

Question 1

What is a motor unit?

Answer 1

One motor neuron innervates one group of muscle fibers

Question 2

What happens to cause an action potential in the muscle fiber?

Answer 2

Motor neuron releases ACh

AChRs allow influx of Na and efflux of K

Leads to activation of v-g Na channels and action potential propagation

Question 3

What is the end-plate current?

Answer 3

Entrance of Sodium ions into the muscle fiber

Question 4

What is the end-plate potential?

Answer 4

The change in muscle fiber potential, more than enough to produce a postsynaptic action potential

Question 5

What are miniature end plate potentials?

Answer 5

Like EPPs, but much smaller in amplitude

Caused by spontaneous release of quanta of ACh

Question 6

What is the safety factor?

Answer 6

Difference between the actual EPP and threshold potential required to generate muscle action potential

EPP is more positive than threshold

Question 7

What is the structure of a nicotinic AChR?

Answer 7

5 subunits arranged around a central pore

2 a, 1 B, y, and delta

Question 8

What is characteristic of an embryonic AChR?

Answer 8

Longer single channel mean open time and lower single channel current

Question 9

What is characteristic of an adult AChR?

Answer 9

Shorter single channel mean open time and greater single channel current

Question 10

How does the motor neuron know where to form synapses?

Answer 10

Motor neuron releases ACh before making contact

Muscle membrane responds to ACh before contact

Synapses form where these interactions take place

Question 11

Where are AChRs located before innervation?

Answer 11

Aggregate in center of developing muscle fibers

Question 12

How does the nerve induce increased clustering of receptors?

Answer 12

Preexisting receptors are redistributed

New receptors are synthesized

Turnover is decreased

Question 13

What is the function of agrin?

Answer 13

Released by the nerve

Initiates AChR clustering by regulating the interaction of MuSK and LRP4

Question 14

What is the function of Dok-7?

Answer 14

Required to activate MuSK after binding of agrin and thus aggregate AChRs

Question 15

What is the function of rapsyn?

Answer 15

Binds to AChRs and aggregates them to synapses

Other components of NMJ co-cluster with AChRs

Question 16

What occurs after innervation?

Answer 16

Receptor half-life increases, embryonic receptors disappear and adult receptors appear

Question 17

How are excess innervations by other motor neurons eliminated in the developing NMJs?

Answer 17

In neuron that will be eliminated, number of receptors on muscle is reduced –> decrease in synaptic strength causes further loss of receptors –> cycle eventually leads to terminal withdrawal

Question 18

What is the function of botulinum toxin?

Answer 18

Blocks ACh release

Question 19

What is the function of curare and bungarotoxin (snake venom)?

Answer 19

Inhibits AChRs

Question 20

What is the function of physostigmine and neostigmine?

Answer 20

Inhibits AChE

Question 21

What is the function of tetrodotoxin?

Answer 21

Blocks Muscle Na channels

Question 22

What is the function of Conotoxins?

Answer 22

Block neuronal Ca channels, muscle Na channels, and AChRs

Question 23

Describe Myasthenia gravis

Answer 23

Most patients have antibodies against AChRs, some to MuSK

Causes reduced AChRs at NMJ

EPPs and MEPPs are smaller than normal

Question 24

What are the clinical features of Myasthenia gravis?

Answer 24

Weakness and fatigue of voluntary muscles

Worsens on exertion

Ocular muscle weakness

Question 25

What are the treatments for MG?

Answer 25

AChE inhibitors Drugs to reduce immune response Removal of AChR antibodies

Question 26

Describe Lambert-Eaton syndrome.

Answer 26

Antibodies against presynaptic Ca channels Affects primarily limb muscles Exercise improves weakness

Question 27

What are the congenital myasthenic syndromes?

Answer 27

AChRs Dok7 MuSK rapsyn LRP4

Question 28

Describe botulism

Answer 28

Caused by Clostridium botulinum Affects autonomic nervous system as well as NMJ Death can occur from respiratory muscle paralysis

Question 29

What is botulinum toxin used to treat?

Answer 29

Muscle contractures and spasms, strabismus (cross-eyes) and headaches

Question 30

How does ageing affect the NMJ?

Answer 30

NMJ becomes unstable over time Synaptic area decreases as AChRs fragment and number of postsynaptic folds decreases Eventually lose motor nerves Reinnervation is less likely to occur