Pharmacology

Question 1

Are the branches of a motor neuron axon myelinated or unmyelinated as they reach the muscle?

Answer 1

motor neurone axon divides into unmyelinated branches near to the muscle

Question 2

What is the name given to the terminal point of each branch of the motor neuron axon?

Answer 2

terminal bouton

forms a chemical synapse with the muscle membrane at NMJ

Question 3

What does an AP travelling down the motor neuron axon to the terminal bouton cause?

Answer 3

release of the transmitter acetylcholine (ACh)

Question 4

What cells surround the terminal bouton?

Answer 4

Schwann cells

Question 5

What is the name given to the membrane of the motor end plate?

Answer 5

Sarcolemma

Question 6

Where do synaptic vesicles of ACh wait until they are released?

Answer 6

Synaptic vesicles await release in clusters at active zones

Question 7

WHat receptors are responsible for the uptake of ACh

Answer 7

Nicotinic ACh receptors

Question 8

How is ACh synthesised?

Answer 8

Active transport of choline into terminal bouton

Choline + acetyl CoA = ACh
(mediated by Choline acetyl transferase enzyme)

ACH transported into vesicle

Question 9

How is ACh released from the vesicles?

Answer 9

AP opens Ca channels on terminal bouton

Ca in terminal causes exocytosis of vesicles in active zones

Question 10

What does ACh allow the nicotinic receptor to do?

Answer 10

Binds to specific binding sites which allow receptor to open
=> Na IN and K OUT

Question 11

What enzyme is responsible for degradation of excess neurotransmitter in the synaptic cleft?

Answer 11

Acetylcholinesterase

Question 12

Describe the structure of a nicotinic receptor

Answer 12

Pentamer

Subunits

• 2x alpha
• beta
• delta
• gamma

forms cation selective pore (=> positive ions flow through centre)

Question 13

How is the end plate potential (e.p.p.) generated?

Answer 13

The driving force for Na+ > K+ at resting membrane potential

=> influx of Na+ > efflux of K+

=> depolarization known as the E.P.P

Question 14

How is the amount of neurotransmitter in one vesicle defined?

Answer 14

each vesicle contains one ‘quantum’ of neurotransmitter

Question 15

What occurs if an e.p.p exceeds threshold?

Answer 15

e.p.p that exceeds threshold triggers an ‘all or none’ propagated action potential that initiates contraction

Question 16

What does the AP arriving at the T-Tubules induce?

Answer 16

Triggers release of Ca2+ from the SR

=> causes contraction by interacting with troponin associated with the myofibrils

Question 17

What category of drugs are responsible for inhibiting AChE?

Answer 17

anti-cholinesterases - reversibly block action of AChE

Question 18

What are the symptoms of Neuromyotonia (NMT, or Isaac’s syndrome) ?

Answer 18

cramps
stiffness
slow relaxation (myotonia)
muscle twitches (fasiculations)

Question 19

What is thought to be the cause of Neuromyotonia?

Answer 19

autoimmune antibodies against voltage-activated K+ channels in the motor neurone

=> hyperexcitability (repetitive firing)

Question 20

What treatments are usually given in neuromyotonia?

Answer 20

anti-convulsants (e.g. carbamazepine, phenytoin) which block voltage-activated Na+ channels
=> less Na influx to create e.p.p

Question 21

Describe the common symptoms of Myasthenia Gravis

Answer 21

progressively increasing muscle weakness during periods of activity

weakness of the eye and eyelid muscles

Question 22

What is the cause of Myasthenia Gravis

Answer 22

autoimmune antibodies against nicotinic ACh receptors in endplate

=> reduction in the number of functional channels and hence reduced amplitude of the e.p.p.

Question 23

What treatments can be used for myasthenia gravis?

Answer 23

anticholinesterases (increase conc. of ACh in cleft)

• edrophonium for diagnosis
• pyridostigmine for long term Tx

immunosuppressant agents
- azathioprine

Question 24

What is the cause of Botulinum Toxin?

Answer 24

exotoxin toxin (related to tetanus and diptheria)

• acts at motor neurone terminals to irreversibly inhibit ACh release
• enters presynaptic nerve terminal to enzymatically modify proteins involved in the docking of vesicles containing ACh (therefore preventing exocytosis)

Question 25

What class of drugs are ineffective as therapy against botulinum toxin?

Answer 25

anti-cholinesterases are ineffective as therapy

Question 26

Give an example of when a low dose version of botulinum toxin is clinically used?

Answer 26

Low dose botulinum haemaglutin complex = administered by IM injection to treat overactive muscles
e.g. extraocular muscles in ‘squints’

used to smooth out wrinkles too!

Question 27

What is the function of ‘curare-like’ compounds? (e.g. vecuronium, atracurium)

Answer 27

competitive antagonists of the nicotinic ACh receptor

=> Reduce amplitude of e.p.p. to below threshold for muscle fibre AP generation

=> can induce reversible muscle paralysis in certain types of surgery

Question 28

What are the common symptoms of Lambert-Eaton Myasthenic Syndrome (LEMS)?

Answer 28

muscle weakness in the limbs, very rare and associated with small cell carcinoma of the lung

Question 29

What causes Lambert-Eaton Myasthenic syndrome?

Answer 29

autoimmune antibodies against voltage-activated Ca2+ channels
=> reduced Ca2+ entry in response to depolarization
=> reduced vesicular release of ACh

Question 30

What is used to treat Lambert-Eaton Myasthenic Syndrome?

Answer 30

anticholinesterases
- pyridostigmine

potassium channel blockers
- 3,4-diaminopyridine

=> increase concentration of ACh in the synaptic cleft