ND3: Synaptic release Flashcards
How is a signal passed from nerve to muscle?
The action potential is initiated at the axon hillock
The local circuit theory causes the movement of signal from nerve to muscle with no loss of amplitude
What is the neuromuscular junction?
The synapse between a nerve and a skeletal muscle fibre
What type of synapse is a neuromuscular junction? Why?
Chemical synapse
Involves the release of a chemical, e.g. acetylcholine
Why are there lots of voltage-gated Ca2+ ion channels at the presynaptic membrane?
They are crucial for transmitter release
What effect does depolarisation have on Ca2+ channels?
It opens them
What happens when voltage-gated Ca2+ ion channels are activated?
The release of transmitter from nerve terminal is initiated
What are vesicles?
Small membrane-bound spheres containing large concentrations of acetylcholine
What happens at the nerve terminal?
- The voltage-gated Ca2+ ion channels are closed at the resting potential
- Action potential arrival opens the voltage-gated Ca2+ ion channels
- Ca2+ enters and triggers the release of transmitter
How can the Ca2+ influx through ion channels cuase such a large increase in [Ca2+]i?
The concentration of Ca2+ inside is so low, so even a small increase in ions will raise the concentration significantly
Why does the Ca2+ concentration need to be so tightly controlled?
Involved in muscle contraction, release of hormones, and release of transmitter
How can more neurotransmitter be released?
By having multiple action potentials in quick succession, which will cause a huge influx of Ca2+ and therefore lots of release of transmitter
Why are multiple action potentials required to release more transmitter?
Because action potentials are only one size so there cannot be ‘bigger action potentials’
With respect to K+ and Na+ channels, how quickly do Ca2+ channels activate and inactivate?
More quickly than K+ channels but more slowly than Na+ channels
Why can Ba2+ be used as a model for Ca2+ channels?
It will pass through the pore of Ca2+ channels
Compare the inactivation of Ca2+ channels when Ca2+ and Ba2+ flow through the channel. What does this suggest?
When Ba2+ flows through the channels, much less inactivation is seen
This suggests that increased intracellular Ca2+ concentration leads to inactivation of Ca2+ channels
What are motor end plates?
The sites where muscle mibres make contact with axons
For what are motor end plates responsible?
Transmitting the signal from the nerve to the muscle
What is the role of mitochondria at the neuromuscular junction?
Take up Ca2+, otherwise transmitter would be released at all times
What is the role of Schwann cells?
Provides the cell with its myelin sheath
What is the role of acetylcholinesterase?
Breaks down acetylcholine very quickly to make sure it doesn’t activate the receptor for too long
What is the role of acetylcholine receptors on the postsynaptic muscle membrane?
Acetylcholine binds to them to carry on the signal from the nerve to the muscle
What is the process of transmitter release?
-
Ca2+ entry through voltage-gated Ca2+ channels
- Significant increase due to low Ca2+ concentrations
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Ca2+ binds to synaptotagmin
- Brings vesicles closer to the nerve membrane
-
Snare complex makes a fusion pore
- Forms a pathway between the vesicle and the synaptic cleft
- Transmitter released through this pore
To what receptors does acetylcholine bind?
Nicotinic acetylcholine receptors (nAChR)
What type of channel is nAChR?
A ligand-gated cation-specific ion channel
How is the skeletal muscle depolarised?
- ACh diffuses across the synaptic cleft thus increasing the concentration of ACh
- Two molecules of ACh bind to nAChR causing a conformational change
- The pore of nAChR opens and allows Na+ in and K+ out at equal rates
- Na+ influx predominates over K+ efflux because the resting potential is much closer to EK than ENa
- This causes depolarisation
How does the structure of the nicotinic receptor affect the depolarisation of skeletal muscle?
- The nicotinic receptor has five subunits (2α, 1β, 1γ, 1δ)
- Each α subunit has a binding site for ACh (hence the need for two ACh molecules)
- The binding of ACh causes the diameter of the pore to increase, so ions can flow through and depolarise the endplate of the muscle
What happens to the endplate potential if the external Ca2+ concentration is decreased?
The endplate potential will decrease because the transmitter release is dependent on Ca2+ entry
How does d-tubocurarine (d-TC) act as a competitive block?
It fits into the binding sites of the nAChR, preventing ACh from binding
Threshold is not reached, therefore there will be no action potential generated, therefore paralysis occurs
How can the competitive block caused by d-tubocurarine (d-TC) be overcome?
By increasing the concentration of ACh which increases the chance of ACh finding available binding sites
What are the two types of neuromuscular block? Give an example of each.
Competitive block, e.g. d-tubocurarine (d-TC)
Depolarising block, e.g. succinylcholine
How does succinylcholine act as a neuromuscular block?
- When succinylcholine is released, the nAChRs will still be activated, but ACh will not be broken down by AChE
- This results in a prolonged depolarisation at the neuromuscular junction resulting in continuous activation of the Na+ channels
- Adjacent Na+ channels will become inactivated so the depolarisation is maintained and no action potential will be generated
