Fundamental Principles Of Synaptic Transmission Flashcards
Give the basic steps in synaptic transmission
- Synthesis
- Creation of intermediate storage
- Creation of vesicle release
- Fusion of vesicle with cell membrane so the intermediate moves into the synapse
- inactivation
- uptake
What blocks the sodium channel?
Lignocaine
Give the steps of the release of vesicle contents into the synapse
1- action potential reaches axon terminals
2- voltage gated ca2+ channels open
3- ca2+ binds to sensor protein in cytoplasm
4- ca2+ Protein complex stimulates fusion and exocytosis of neurotransmitter
What does SNARE stand for?
Soluble N-ethyl maleimide-sensitive factor Attachment protein Receptor
Where would you find a v-SNARE?
On vesicle plasma membrane
Where would you find a t-SNARE?
On the targets plasma membrane
Give the names of the two v-SNAREs
Synaptobrevin
Synaptotagmin
What does synaptotagmin sense?
Calcium
What is synaptobrevin (apart from a v-SNARE)
Vesicle associated protein = VAMP
Give the names of the two t-SNAREs
Syntaxin -1
SNAP 25
What happens with the SNAREs when there is in increase in calcium?
It is bound by synaptotagmin, leads to a higher affinity for the cell membrane and a reduced affinity for v-SNAREs
What is a SNAREpin
V-SNARE and t-SNARE interaction
What does a SNAREpin do?
Pulls the vesicle closer to the membrane
What does botulinum toxin do?
Binds to glycoproteins found on cholinergic neurones, then the peptidase breaks down the V and T-SNAREs
What does betabungarotoxin do?
Binds to glycoproteins found on cholinergic neurones, then the peptidase breaks down the V and T-SNAREs
What is calcium dependant release in synapses?
- Calcium binds to a lobe of the synaptotagmin
- increased affinity for phospholipids
- binding causes increased membrane curvature
- forced interaction of synaptobrevin and syntaxin 1/SNAP25
- residue fusion with membrane
What is the botulinum toxin produced by?
The anaerobic bacterium clostridium botulinum
What is the minimum lethal dose of the botulinum toxin in mice?
10^-12
How many subunits make up the botulinum toxin?
2
Which botulinum toxins cleave SNAP 25?
A, C, E
Which botulinum toxins cleave VAMP?
B, D, F, G
Give the steps in cholinergic neuronal transmission
- choline is take up alongside sodium
- choline -> acetylcholine by choline acetyltransferase
- rest of pathway Same as normal
Why is the cholinergic response short acting?
The amount of acetyl cholinesterase in the synaptic cleft
What does the acetylcholine react with on the receptor membrane?
Nicotinic LGICs or GPCRs
How does hemicholinium inhibit synaptic transmission?
Competes with choline for uptake
How does vesamicol inhibit synaptic transmission?
Stops uptake of acetylcholine into a residue
How do toxins inhibit synaptic transmission?
Stop fusion of vesicle with cell membrane
Give the name of the short acting cholinesterase inhibitor.
Edrophonium
Give the names of the medium acting cholinesterase inhibitors.
Neosigmine
Physostigmine
Give the names of the irreversibly acting cholinesterase inhibitors.
Parathion
Ectothiophate
Dyflos
What happens in adrenergic neurones in the adrenal glands?
- Uptake of tyrosine which after a number of steps is converted to adrenaline by phenylethanolamine N-methyltransferase
What happens in adrenergic neurones in the body (not adrenal glands)?
Uptake of tyrosine which is then converted into catechol-o-methyltransferase
What happens to noradrenaline in the synaptic cleft?
Inactivated by extraneuronal cells or back into the neurone by a neuronal transporter
How does reserpine inhibit synaptic transmission?
Stops the noradrenaline uptake into vesicles
How does guanethidine inhibit synaptic transmission?
Displaces noradrenaline in the vesicle
How do cocaine, desipramine and imipramine inhibit synaptic transmission?
Inhibit the noradrenaline uptake
How do amphetamine, tyramine and ephedrine inhibit synaptic transmission?
Competitive inhibitor for the reuptake of noradrenaline back into the nerve. Can also displace noradrenaline in the vesicle
