Module 9 - synapses Flashcards
Electrical synapses: what are they and why are they not always used
Gap junctions between synapses that allow for direct transfer of ions
Cannot turn an excitatory signal in one neuron into an inhibitory signal in another - they lack versatility, flexibility, and capacity for signal modulation
Key factors to vesicular release
Sometimes contain an uptake system either for the neurotransmitter directly or the products broken down by enzymes (this uptake system can instead be taken up by glial cells)
Contains a lot of mitochondria as it is a large energy-consuming process (this is why the brain uses so much energy)
Vesicular release: the process
SNARE proteins:
Synaptobrevin, attached to the vesicle containing the neurotransmitters, binds to SNAP-25 and syntaxin in the membrane and causes the vesicle to be ‘docked’ into the active point of the Presynaptic membrane
Once synaptobrevin detects an increase in intracellular calcium channels, the vesicle fuses with the membrane, releasing the contents
Quantal neurotransmitter release
Fixed amounts of neurotransmitters are released in integer amounts (from 1x to 8x)
Evoked vs non-evoked release
Evoked: due to calcium ions causing vesicular release, high quantal release (may be up to 200 quanta, each containing several thousand neurotransmitters)
Non-evoked: Occur spontaneously, low quantal release
Vesicle recycling: what facilitates recycling and what does it allow for?
Clathrin (football structure - 20 hexagons, 12 pentagons) causes vesicles to form and moves them into the cell for neurotransmitters to refill the vesicle
The cage is always a consistent size, allowing for consistent size, a consistent neurotransmitter amount, a consistent vesicular amount and a consistent terminal size (prevent membrane bagginess)
Toxins - ω-conotoxin MVIIA: where is it obtained from, what does it do, and what other key factors are there?
Obtained from the magician cone snail (Conus magus)
This toxin blocks N-type voltage-gated calcium channels, stopping neurotransmitter release.
- Conotoxins are very selective for their target proteins so have been useful in working out, for example, which types of voltage-sensitive calcium channels are present in a synapse
- There are also α-conotoxins in Conus magus venom (these block nicotinic acetylcholine receptors)
ω-conotoxin: how is it used by cone snails, what is its structure, and how can we use it?
Cone snails are predatory marine snails - they harpoon their prey and pump a cocktail of peptide toxins into them, paralyzing them.
All conotoxins are small peptides with disulphide bridges
A synthetic version of ω-conotoxin MVIIA, called ziconotide, is injected into the spine to treat types of pain that resist other medications e.g. cancer pain.
Toxins - ω-agatoxin IVA: where is it obtained from, what does it do, and what other key factors are there?
Obtained from the funnel web spider (Agelenopsis aperta)
This toxin blocks P/Q-type voltage-gated calcium channels, stopping transmitter release
it binds to a different type of calcium channel to the ω-conotoxins: P/Q type instead of N-type
ω-agatoxin: how is it used by funnel web spiders and how can we use it?
Like cone snails, the funnel web spider uses its toxin to subdue its prey
It is a further tool in our arsenal for working out which calcium channels are present in particular synapses.
Toxins - calabar bean: where is it obtained from, what does it do, and what other key factors are there?
Obtained from Physostigma venenosum containing the acetylcholinesterase inhibitor physostigmine (also known as eserine)
It stops the breakdown of acetylcholine, which shuts down neuromuscular transmission as the nicotinic receptor becomes desensitized
Calabar bean: how can we use it?
Physostigmine can be used to treat the muscle disease myasthenia gravis
It can also help reverse the effects of toxins that bind to the acetylcholine binding site e.g. curare
Myasthenia gravis (MG) is an autoimmune disease in which nicotinic receptors are attacked by antibodies - It causes muscle weakness and drooping eyelids are a common symptom
Inhibitors of acetylcholinesterase can treat MG by boosting acetylcholine concentrations
Toxins - Botulinum: where is it obtained from, what does it do, and what other key factors are there?
Produced by the anaerobic bacterium Clostridium botulinum, it is a proteolytic enzyme that cleaves SNARE proteins, stopping vesicles from docking with the membrane, which prevents neurotransmitter release.
Botox is the most deadly toxin known to man - its LD₅₀ (amount needed to wipe out half of a species’ population) in humans is estimated to be around 2 ng/kg
Calabar bean: how can we use it?
- Botulinum toxin is famous for its use as a wrinkle remover. However, it also has clinical uses for treating migraine, muscle spasms, excessive sweating and squints. In these uses, it is injected into a small area of muscle to prevent systemic effects
- Produces muscle weakness and paralysis and is frequently fatal.
Toxins - α-bungarotoxin and α-cobra toxin: where are they obtained from, what does it do, and what other key factors are there?
Obtained from the banded krait (Bungarus multicinctus)
Blocks nicotinic acetylcholine receptors, binding almost irreversibly to the nicotinic receptor, stopping its activation and blocking the endplate potential.
- These toxins are members of the alpha neurotoxin family
