M&R Neurotransmission

Question 1

Describe nicotinic ACh receptors.

Answer 1

Ligand gated ion channel that requires the binding of 2 ACh molecules in order to open.
It lows passage of sodium and potassium.

Question 2

How do we know neurotransmitter release is dependent on calcium?

Answer 2

Reducing extracellular calcium concentration results in a smaller end plate potential, which indicates that less neurotransmitter has been released.

Question 3

Give 2 types of blocker of the nAChR.

Answer 3

Competitive - d-tubocurarine

Depolarising - succinylcholine

Question 4

Describe how competitive blockers work.

Answer 4

D-tubocurarine binds directly to ACh binding sites, but does not cause nAChR channels to open.
It blocks ACh from binding.
This results in less depolarisation with the same concentration of ACh.
The binding of d-tubocurarine vs. ACh is dependent on their relative concentrations.

Question 5

Describe how depolarising blockers work.

Answer 5

Succinylcholine binds to nAChR causing the channel to open.
Succinylcholine is not degraded well by AChE.
Thus, it results in sustained depolarisation that leads to inactivation of voltage gated sodium channels.
When inactive, v-gated sodium channels are non conducting and so AP cannot be stimulated.
This also results in receptor desensitisation.

Question 6

What is mature end plate potential?

Answer 6

ACh released into cleft spontaneously at 1 vesicle/s.

This results in a small, detectable depolarisation that does not reach threshold.

Question 7

Describe the fault in myasthenia gravis

Answer 7

Autoimmune destruction of nAChR at the motor end plate caused by antibodies:
Complement mediated lysis
Receptor degradation.
End plate potentials are weak

Question 8

How is myasthenia gravis treated

Answer 8

AChE inhibitors raise the ACh concentration in the cleft.

Question 9

End plate potential in myasthenia gravis

Answer 9

Decreased amplitude due to fewer nAChR to bind and cause depolarisation.

Question 10

How does ACh stimulate contraction?

Answer 10

2 ACh bind to nAChR on the motor end plate.
This causes opening of the channel associated with the receptor, which allows passage of sodium and potassium.
Sodium influx causes depolarisation to threshold.
This spreads by local current causing voltage gated sodium channels to open resulting in transmission of he action potential along the motor end plate and down into T tubules where it causes calcium release from sarcoendoplasmic reticulum.
This binds to troponin, which causes it to shift tropomyosin uncovering the myosin head binding site in actin, leading to the power strike of contraction.