M&R Session 5 (Lecture 5.1) Flashcards Preview

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Flashcards in M&R Session 5 (Lecture 5.1) Deck (16):

What does depolarisation in the nerve terminal cause?

Opens VGCCs allowing Ca2+ influx


What does an influx of calcium cause in the nerve terminal?

Release of neurotransmitter


Name two DHPs and what they block?

Nifedipine and nicardipine blocks L-type VGCC.


What is the general structure of VGCCs?

4 subunits (T6m) with one subunit needed to be functional


What do the other subunits in the VGCCs do? What does phosphorylation do to the channel?

1) Modulate channels

2) Increase activity via kinases


What is the break down products of acetylcholine and by which enzyme?

Choline + Acetate

Acetylcholine esterase


What type of receptor is the nAChR? What flows through the channel?

Ligand-gated allowing flow of cations e.g. Na+ influx with K+ efflux.


How is acetylcholine synthesised and released?

1) Acetyl CoA from the mitochondria and choline (import via Na+-dependent choline transporter) is used to synthesise ACh via choline acetyltransferase
2) ACh is transported into small clear vesicles by the vesivle associated transporter with efflux of H+ (antiport)
3) When VGCCs open and calcium enters the cell, vesicles migrate towards the membrane which bind to synaptotagmin.
4) This complex interacts with the SNARE complex specifically SNAP 25 which creates a pore whtough which ACh can be released.


How many molecules of ACh must be attached to the nAChR to cause opening?



What is the membrane potential change in the postsynaptic membrane? What happens at the peak of depolarisation?

-90 to -10mV (peak = no net flow of ions)


What is an end-plate potential? How can it be changed?

ACh acting on nAChR recorded from the muscle fibre

End plate potentials decrease in amplitude as external Ca2+ is lowered


What does the end plate potential cause in the postsynaptic membrane?

Activate adjacent Na+ channels due to local spread of charge causing a muscle AP. The resulting AP conducts away from the receptor.


Describe the MOA of tubocurarine and suxamethonium/succinylcholine?

1) Tubocurarine - competitive blocker of the nAChR. (can be reversed with high [ACh]

2) Suxamethonium - depolarising blocker agonist (binds to nAChR causing depolarisation and maintenance of this state so no further APs can be generated). Inactivates Na+ channels and is not broken down by AChE


How are miniature end plate potentials generated?

Spontaneous release of vesicles. Also known as quanta release. Causes a mepp, spike of 1mV


Describe the symptoms of MG.

Profound weakness
Weakness increases with exercise
EPs are reduced in amplitude leading to muscle weakness and fatigue

(Caused by Ab directed towards nAChRs on skeletal muscle leading to loss of these receptors by complement mediated lysis and receptor degradation)


Why is a nAChR faster than a mAChR?

nAChR - intrinsic ion channel

mAChR - GPCR leading to enzyme cascade activation