Measuring Drug Action at NMJ

Question 1

Where is acetylcholine released in skeletal muscle?

Answer 1

At the synapse between .the neuron and muscle. It then combines with nicotinic acetylcholine receptors

Question 2

What happens at neuromuscular synapses?

Answer 2

• Acetylcholine molecules are stored in vesicles in the presynaptic terminal.
• An incoming action potential causes the vesicles to fuse with the cell membrane and release acetylcholine
• Acetylcholine molecules bind to nicotinic receptors on the post-synaptic cells

Question 3

How do skeletal muscles contract?

Answer 3

• Nicotinic ach receptors are ligand-gated ion channels
• Activated by an influx of Na+ ions
• Depolarisation due to an increase in membrane potential
• Muscle contraction

Question 4

How is the response terminated?

Answer 4

• ACH broken down by acetylcholinesterase
• Acetate + choline
• Terminates the action acetylcholine
• Choline- transported back into the presynaptic terminal
• Choline combines with acetyl-CoA to form acetylcholine again

Question 5

What are clinical uses of curare?

Answer 5

• Muscle relaxant (anaesthesia)
• Lighter anaesthesia (can be used with relaxation of muscles of abdomen and diaphragm)
• Relax vocal cords (tracheal intubation and mechanical ventilation in intensive care)

Question 6

What are acetylcholinesterase inhibitors?

Answer 6

Inhibit the cholinesterase enzyme from breaking down ACh

Question 7

What is an example of a slowly reversible ACH-sterase inhibitor?

Answer 7

Neostigmine - slow to leave active site

Question 8

What is an example of an irreversible ACHstrase inhibitor?

Answer 8

Sarin - forms a covalent bond with enzyme = permanent inactivation. Cannot produce ACH.

Question 9

Why does Sarin gas/Novichok kill?

Answer 9

Sarin raises ACh levels , overstimulates and causes a depolarising block.

Question 10

What are the therapeutic actions of ACHsterase inhibitors?

Answer 10

• PYRIDOSTIGMINE/NEOSTIGMINE - antidote for curare poisoning.
• used for myasthenia gravis (autoimmune condition) - antibodies against nicotinic receptors.
• antibodies inactivate some of the nicotinic acetylcholine receptors.

Question 11

What are the therapeutic actions of ACHsterase inhibitors (2)?

Answer 11

-Donepezil , tacrine, galantamine and rivastigmine for Alzheimer’s.