Synaptic Transmission At Neuromuscular Junctions Flashcards
What is a neuromuscular junction?
A synapse between a nerve and skeletal muscle fibre.
What three ion channels are present in the end plate of an axon terminal?
Ca2+
Na+
K+
How are calcium voltage-gated ion channels structured?
4 subunits: I, II, III, IV along the plasma membrane.
Also have an alpha pore forming subunit for functional control.
Do Ca2+ activate faster or slower than Na+ channels?
SLOWER
What type of cell surrounds the nerve axon?
A Schwann cell (myelin sheath)
Explain Ca2+ released into the nerve axon causes vesicles of AChR to be released into the synaptic cleft?
Ca2+ enters through the voltage gated channels and binds to SYNAPTOTAGMIN.
This causes the SNARE COMPLEX to create a fusion pore, releases the contents of the vesicles (the transmitter) out of the axon.
How many AChR molecules bind to the nAChR causing a conformational change and Na+ to be released.
2
What is the name of the enzyme that hydrolyses AChR soon after its release?
ACh esterase
How do depolarising blockers work?
Act as ACh receptor AGONISTS.
Bind to receptor and generate an action potential.
The blockers are not metabolised by ACH esterase, which results in prolonged depolarisation at the end plate.
This leads to inactivation of Na+ channels.
The axon cannot repolarise resulting in a phase 1 block.
How do non-depolarising agents work?
Act as competitive antagonists.
Bind to ACh receptors so ion channels cannot open and depolarisation cannot occur.
How does the drug d-Tubocurarine work? Can it be overcome?
A competitive blocker - non - depolarising.
However it can be overcome if you increase the concentration of ACh - effects will be less extreme.
How does the drug Succinycholine work?
A depolarising blocker.
Causes maintained depolarisation and mimic ACh without being hydrolyses by ACh esterase.
Leads to Na+ channel inactivated and DESENSITISATION.
How does the condition Mayathenia Gravis affect nACh receptors?
An autoimmune condition where antibodies attach nAChR on the post-synaptic membrane of the skeletal muscle.
Muscle cells never reach the threshold of action potential and patients have profound muscle weakness and gets worse with exercise.
Explain step by step the journey from when in impulse arrives at the axon terminal into a chain of muscle contractions.
The arrival of an impulse on the end plate causes voltage-gated Na+ and Ca2+ channels to open, depolarising the axon.
Ca2+ molecules the bind to the ACh vesicles, causing them to leave the axon via exocytosis into the synaptic cleft.
Two ACh molecules bind to the nACh channels on a voltage=gated Na+ channel on a nearby muscle cell, causing it to open and Na+ to be released into the cell.
This influx of Na+ triggers the Ca2+ channels on the muscle cell to open, causing influx of Ca2+.
An increase in the concentration of Ca2+ in the cell initiates the opening of the sacroplasmic reticulum, releasing even more Ca+ through a ‘calcium induced calcium released’ process.
This causes the cell to contract, and gap junctions between cells communication cell contraction, a domino effect.
How do mAChRs differ from nAChRs?
NAChRs produce fast depolarisation through ligand gated ion channels.
MAChRs produces a much slower response.
They use G-proteins to trigger a cascade of effects in the cell.
As AChR molecules bind to the maChR in the cell surface, this the Ga and By subunits to disassociate. The G subunit then binds to the target effector, triggering a action potential.
MAChRs are present on target tissues, not neurones.
