Synaptic transmission and the neuromuscular junction Flashcards
What is a neuromuscular junction?
A neuromuscular junction is the synapse between a nerve and a skeletal muscle fibre.
What ion channels are in the nerve terminal?
Voltage-gated Na+ channels
Voltage gated K+ channels
Voltage gated Ca2+ channels
What happens at the nerve terminal?
- Depolarisation occurs
- Open voltage gated Ca2+ channels
- Ca2+ entry
- Increase Ca2+ conc (usually very low so, entry produces significant increase in conc.)
- Release of neurotransmitter
What is the structure of a Ca2+ channel?
Similar to a Na+ channel. It consists of one subunit containing 4 similar repeats wherefore creating a ring structure.
Each repeat contains 6 membrane spanning segments. The 4th membrane spanning segment is a voltage sensor and there is a pore between the 5th and 6th.
There are many different types of Ca ion channels. There are more than just the alpha subunit involved in making the channel. (some inc. phosphorylation).
What are some properties of Ca2+ channels?
Voltage gated Ca2+ channels activate more slowly than voltage gated Na+ channels
Ca2+ channels activate and inactivate -but much more slowly than Na+ channels
Ca2+ channel inactivating is Ca2+ dependant
In a neuromuscular junction, what receptors are present on the post synaptic muscular membrane?
Nicotinic Acetylcholine Receptors. These are ligand gated ion channels as opened by a ligand (ACh).
How is neurotransmitter released into the synaptic cleft?
- Ca2+ enter though Ca2+ channels
- Ca2+ binds to synaptotagmin (a protein
- Synaptotagmin helps to bring the vesicle of ACh close to the membrane (forms a snare complex)
- A snare complex then makes a fusion pore
- Neurotransmitter (ACh) is then released though this pore via exoctosis.
What happens when ACh binds to its receptor?
You need two ACh to bind to each nicotinic ACh receptor.. Once this happens, a conformational change occurs which opens the channel. This channel is a cation selective pore so let positive ions through.
Why does the opening of the ACh cation selective channel, that lets both Na+ in and K+ out cause depolarisation?
This is because the resting potential of the cell is about -70mV which is much closer to Ek (equilibrium potential of K) than that of Na. Therefore, more Na will flow in, and make the cell more positive, than K+ will flow out. This local depolarisation is called end plate potential.
What happens when an end plate potential releases threshold? How?
It generates an action potential in the muscle. ACh binds to nicotinic receptors which causes depolarisation. This spreads to other part of the muscle where there are lots of voltage gated Na+ channels. This then generates an action potential in the muscle. This action potential initiates contraction of the skeletal muscle fibre.
What is curare?
Curare is a resinous dark brown to black mass with a sticky to hard consistency. It causes paralysis by blocking the transmission between nerve and muscle. (neuromuscular blocker used in opus -similar to curare)
What are the two ways nicotinic ACh receptors can be blocked?
Competitive blocker eg curare or tubocurarine
Depolarising blocker er succinylcholine
How does a competitive blocker work to stop the opening of ACh channels?
This ligand is a competitive inhibitor so, it binds where ACh should on the channel. This prevents ACh from binding and therefore, it prevents the channel from opening.
How can competitive blockers be overcome?
Competitive blockers can be overcome by increasing the concentration of ACh. This makes it more likely that ACh will bind and not the inhibitor (d-tubocurarine) so, less channels will be blocked.
How does a depolarising blocker work?
This is when the blocker (succinylcholine) will bind to the nAChR and activate them. It will depolarise the other Na+ channels. You get a maintained depolarisation which means that the Na+ channels will become inactivated so they can no longer open and cause an action potential when ACh does bind.
