Lecture 13 - Synaptic Transmission and the Neuromuscular Junction

Question 1

how do we pass a signal from a fired nerve to a muscle

Answer 1

neuromuscular junction - presynaptic cleft and a postsynaptic membrane

depolarisation from an AP on the neuron will cause voltage gated Ca2+ channels to open at the nerve terminal

Ca2+ will flow into the nerve terminal
the increased Ca2+ concentration will promote exocytosis

the neurotransmitter is released into the synaptic cleft

the internal Ca2+ conc is very low so we only need a small Ca2+ influx to bring a large conc change to trigger exocytosis - extra info

if we increase the frequency of AP’s increases the amount of nerve terminal Ca2+ entry

Question 2

what is the structure of the voltage gated Ca2+ channels ?

Answer 2

the same structure as a Voltage gated sodium channel

we have a diverse range of Ca2+ throughout the body that may be inhibited by many different things

Ca2+ channels activate and deactivate slower than Na+ channels (like K+)

Question 3

what receptors are involved at the neruomuscular junction (synapse)
how does this process work at the junction ?

Answer 3

Nicotinic Ach receptors are on the post synaptic membrane (we have junctional folds) - ach is degraded in the junction by ach esterase

ach released in vesicle binds and causes it to open

Ca2+ enters pre synapse - binds to synaptotagmin (was holding vesicle in membrane)

vesicle is now released by exocytosis through a fusion pore

the nicotinic ach receptors are permeable to cations - Na+ and K+

this can cause a depolarilasation activating Voltage Na+ channels in post synaptic membrane and triggering a muscular AP

AP will propagate along the muscle - gives a contraction

Question 4

give and example of a posion and how it works

Answer 4

Curare (a poison) works by blocking transmission between nerve and muscle to cause paralysis

it is a competitive blocker of nicotinic ach
so overcome by increasing ach concentration

Question 5

how can Nicotinic ach be blocked ?

Answer 5

competitively blocked

or depolarization blocker will inactivate channel - this is non competitive - succinylcholine - no muscular AP as it blocks Nach receptors , so Na+ let into muscle and hence no signal

blockers are good to relax muscles for surgery

Question 6

what condition is caused by issues at the neuromusucular junction ? explain this

Answer 6

mayasthenia gravis - autoimmune disease tartgeting Nach receptors

patients get very weak - especially with exercise
as antibodiers attack nAChR on the psot synaptic membrane

nAChR loese function - no longer get AP at muscles - muscle weakness and fatigue

Question 7

explain organophosphate poisoning

Answer 7

achetylcholine esterase breaks down Ach in the neuromuscular junction

organophosphates form a stable (irreversible) complex with the enzyme to inhibit them

recovery takes weeks as we need to rebuild new ach enzymes