neuromuscular blocking drugs

Question 1

somatic NS NMJ pathway

Answer 1

spinal cord (cell body in ventral horn) -> single a-motor neurone axon -> skeletal muscle (ACh)

Question 2

NMJ neuromuscular transmission

Answer 2

a-motor axon -> ACh synthesised by CAT from acetyl CoA and choline in axon and loaded into vesicles -> action potential depolarises -> VGCC open -> Ca2+ influx -> exocytosis of vesicles into cleft -> diffuses to skeletal muscle fibre end plate region (middle of skeletal muscle fibre) -> interacts with and stimulates nicotinic receptors (type 1 as ion channel linked) -> influx of Na+ into skeletal muscle fibre, causing end-plate graded potential -> fires off “all-or-nothing” action potential in both directions of skeletal muscle fibre -> excitation-contraction coupling -> receptor closes within ms -> ACh broken down by AChE; choline actively reuptaken by presynaptic terminal

Question 3

nicotinic AChR in NMJ and significance

Answer 3

2 ACh molecules bind to 2 a subunits in NMJ nicotinic receptors (5 subunits in total); different to ganglionic nicotinic AChR in ANS, so drugs (especially antagonists) developed can have a degree of selectivity to NMJ vs ganglion (different affinities)

Question 4

size of nicotinic AChR in NMJ membrane

Answer 4

span entire membrane with large intra- and extra-cellular domains

Question 5

what ion is lost when nAChR in NMJ open and Na+ influxes

Answer 5

small amounts of K+