Lecture 10- Skeletal Muscle Neurophysiology 2

Question 1

What is the structure of a nicotinic acetylcholine receptor?

Answer 1

• Five subunits, each with 4x transmembrane domains
• Each transmembrane domain has been woven back and forth in the membrane to anchor the receptor in place
• Subunits surround a pore in membrane which is protected from hydrophobia meaning ions can pass through

Question 2

What is the pore contained within a nicotinic receptor usually described as?

Answer 2

Gated- closed off meaning ions can’t pass through

Question 3

How is the pore opened? and what follows as a result?

Answer 3

• The pore is chemically gated and is therefore opened when 2x Ach bind
• The cation ion channel is non-selective and so permeable to both Na+ and K+
• Opening → depolarisation due to Na+ entry

Question 4

Why does the movement of sodium at the pore have more of an effect than potassium?

Answer 4

• Sodium has a favorable concentration gradient + electrical gradient
• Potassium only has a favorable concentration gradient to move out, electricity wise it will want to stay inside the cell because that is negatively charged (opposites attract)
• Therefore, have huge influx of sodium to make cell more positive and only small leakage of potassium out.

Question 5

What happens as a result of prolonged exposure to Acetylcholine at the receptor?

Answer 5

The receptor will shut itself off despite acetylcholine still being bound to prevent continued Depolarisation + action potential propagation into the muscle (the muscle cannot be activated all the time- need a combo of excitation followed by relaxation)

After the gate is desensitized acetylcholine is removed and degraded to allow recycling

Question 6

What is an agonist of the nicotinic acetylcholine receptors?

Answer 6

Nicotine. This means it activates the receptors.

Question 7

What is an antagonist of the nicotinic acetylcholine receptors?

Answer 7

• a-Tubocurarine: from plants (tips of arrows)
• Alpha-neurotoxins: from snakes

Antagonists bind to the channels/ receptors and prevent them from being activated leading to paralysis

Question 8

Acetylcholine must be regenerated by acetylcholinesterase (AchE) in the pre-synaptic terminal of the NMJ BECAUSE choline (rather than acetylcholine) is pumped back to the axon through the choline transporters.

(A) if both statements (the one before and the one after
‘BECAUSE’) are true, and are causally related (the fact
presented in the first statement is a result of the fact
presented in the second statement)
(B) if both statements are true but are not causally related
(C) if the first statement is true and the second is false
(D) if the first statement is false and the second is true
(E) if both statements are false

Answer 8

D)

Question 9

What is Myasthenia gravis?

Answer 9

• Autoimmune (attacking self) disease of NMJ
• Antibodies are produced to muscle nicotine acetylcholine receptors this results in a reduction in the number of receptors due to damage, blocking of the receptors meaning acetylcholine can’t bind and an inflammatory response which damages the end plate of the receptors
• The results is reduced NMJ function → weakness, particularly of frequently used muscles (facial muscles)

Question 10

In myasthenia gravis why do symptoms come on with sustained contraction? And why do AchE blockers help?

Answer 10

• In normal NMJ a rapid sequence of many AP’s in nerve→ slight depletion of releasable pool → less Ach released per AP
• However, normally, still enough Ach released by a single AP to initiate an AP in muscle i.e. high ‘safety factor’.
• However, when # receptors is reduced (as in MG), this normal drop in Ach for later impulses may cause failure of transmission
• Can treat this by delaying breakdown of Ach, so that Ach level builds up. To do this block the enzyme responsible for breakdown of Ach AchE