Acetylcholine

Question 1

Normal muscle contraction

Answer 1

NMJ is point of contact between motor neuron and muscle fibre.
AP arrives and depolarises motor neuron, which opens VG-Ca2+ channels so Ca2+ enters and causes ACh vesicles to dock to membrane, releasing NT into NMJ (exocytosis).

Postsynaptic membrane made of many postjunctional folds; ACh binds to postsynaptic nAChRs (ligand-gated pentameric cation channels) which are clustered at tops of folds. Cations enter postsynaptic cell which causes a local depolarisation (endplate potential) so VG-Na+ channels in lower folds of membrane open and Na+ enters. Large depolarisation causes contraction in muscle fibre.

Question 2

Normal motor endplate

Answer 2

Many of many postjunctional folds which create large surface area.
High density of nAChRs accummulated at crests of folds to maximise response to ACh released into synaptic cleft.
Na+ channels accummulate in troughs of folds.

During development, agrin binds to MuSK and Lrp4 to initiate formation of NMJ and ensuring folds form correctly, with high density of nAChRs clustered at crests of folds. (also maintains during adulthood)

Question 3

Motor endplate in MG

Answer 3

Loss of nAChRs.
Stark reduction in junctional folds, so lower SA of postsynaptic membrane.
Synaptic cleft becomes larger so increased likelihood of ACh being lost to diffusion instead of activating nAChRs.

= reduced integrity of motor endplate, so severe reduction in motor endplate potential amplitudes.