What are the 5 different stages to fast synaptic transmission?
1. AP. 2. Ca influx via calcium channels. 3. Vesicular transmitter release. 4. Activation of transmitter-gated ion channels. 5. Activation of voltage-gated ion channels.
What mediates fast synaptic transmission?
Mediated by transmitter-gated ion channels. eg. nicotinic ACh receptor.
Name the 4 important properties of the nicotinic ACh receptor?
1. Intergral ion channel. 2. Agonist binding to the receptor induces a rapid conformational change to open the channel. 3. Selective for certain ions. 4. Signalling is extremely rapid.
How do you test for fast synaptic transmission?
Record miniature end plate potentials (MEPPS) at the NMJ.
Define what a "MEPP" is?
Miniature end plate potential. It is the energy given off when one single vesicle package of neurotransmitter is released.
What process does the vesicles undergo to release the neurotransmitters from the presynaptic membrane?
What is vesamicol and what does it do?
Inhibits vesicular uptake of ACh and consequently decreases the amplitude of MEPPs.
Name the 2 ways in which a drug can decrease the amplitude of MEPPs?
1. Inhibiting the post-synpatic receptor. 2. Decreasing the amount of ACh in each vesicle.
What way does vesamicol decrease the amplitude of MEPPs?
By decreasing the amount of ACh in each vesicle.
What does alpha-latrotoxin do?
Causes a large ACh release resulting in muscle spasms. Then there is a depletion of vesicles causing paralysis.
Define "quantal content"?
The amount of neurotransmitter in each vesicle.
How are synaptic vesicles recycled?
Exocytosis of neurotransmitter, Endocytosis from the membrane to produce new vesicles. Use of endosome to transport neurotransmitters into the vesicles
What happens during an AP to synaptic release?
Calcium levels increases. Causing an increase in exocytosis- Increase in neurotransmitter release. After AP, low levels of vesicles.
End-plate potential. The energy released taking into account all the vesicles that are released to the end plate.
What does nACh receptor do?
Uses ACh as an agonist to transport sodium into the cell.
What happens to the AP when there is a high magnesium and low calcium extracellular solution?
Reduces the EPP to below threshold for firing an AP.
What happens to the muscle if there is an AP?
Contraction of the muscle.
What does it mean when the release of neurotransmitter is quantal?
There is an immediate release of ACh and then gradually decreases.
What is the equation of the quantal content?
Mean EPP (mV) / mean MEPP (mV)
What receptor is activated to cause a MEPP?
Activation of nicotinic ACh receptors. Each quanta gives rise to this,
A single vesicle.
What does GABAA do?
Mediates miniature inhibitory postsynpatic potentials summate to produce an IPSP-> neuronal inhibition.
What does dendrotoxin (4-aminopyridine) do?
Increase EPP. No change in MEPP. Blocks voltage-gated potassium channels to prolong AP. Increase in calcium influx to increase release.
What does tubocurarine do?
Decrease in EPP and MEPP Acts postsynaptically to block the nicotinic ACh receptors.
What does botulinum toxin do?
Decrease quantal content. Decrease EPP but no change in MEPP. Acts post-synpatically to decrease neurally evoked ACh release.
Name the 4 different stages in which the botulinum toxin inhibit vesicular release?
1. Attachment of the toxin to the postsynpates. 2. Toxin enters the synapse by endocytosis. 3. Light chain is excreted into the cytoplasm. 4. Proteolytic cleavage of synaptobrevin.
A vesicle assocaited membrane protein (VAMP)
Name the 4 different parts in how the botulinum toxin binds to the post-synpases?
Synaptobrevin. Synaptotagmin. SNAP 25. Syntaxin
What part of the binding is Botox B D F G important in?
What part of the binding is botox A E important in?
What part of the binding is botox C important in?
How does synaptotagmin work?
binds to calcium cooperatively and undergoes conformational change.
Describe the 3 stages of a vesicle binding to the postsynpatic membrane?
1. Docking: synaptobrevin binds first to syntaxin and SNAP 25. 2. Priming: Synaptotagmin is recruited to the complex. 3. Fusion: Calcium influx triggers fusion and transmitter release.
What two types of proteins make up the VAMPs?
Synaptotagmin and synaptobrevin.