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SNARE Proteins
SNARE= Soluble NSF Attachment Protein Receptors
Vesicles in releasable pool already attached to axon terminal membrane in active zone
via SNARE proteins
Other vesicles in storage pool attached to cytoskeleton away from active zone
SNARES composed of 3 types of proteins:
Cytoplasmic proteins: NSF and SNAP
Vesicular membrane: v-SNARE (synaptotagmin) and VAMP (synaptobrevin)
Target or terminal membrane: t-SNARE (syntaxin) and SNAP-25
When Ca+ enters axon terminal, Ca++ binds to synaptotagmin, causing it to change
shape
This causes the SNARE proteins to rotate and twist, forming a fusion pore- which will
either flutter open and shut, or invert the vesicle of NT, allowing NT into the synapse
High Ca++ also binds to calmodulin, forming Ca++/calmodulin complexes, which
phosphorylates another protein called synapsin I
When synapsin I is phosphorylated, it releases vesicles in the storage pool from
the cytoskeleton, and moves them up to unoccupied t-SNARES for future release
If enough Ca++ is still present, activates synaptotagmin again, releasing more
NT
Pharmacology of Synaptic Transmission (see fig 3.14 in your book for summary)
1. precursor: L-DOPA is precursor for dopamine
2. inhibit NT synthesis: alpha-methyl-para-tyrosine inhibits tyrosine hydroxylase, so
dopamine and NE are not made
3. block storage of NT in vesicles: reserpine blocks storage of dopamine, NE, and
serotonin
4. stimulate release: amphetamine increases release of dopamine and NE from axon
terminal
5. inhibit release: botulinum inhibits release of NT (degrades SNAP-25)
6. agonist for receptor: nicotine for nicotinic ACh receptors
7. antagonist for receptor: curare is competitive antagonist for nicotinic ACh receptors
8. stimulate autoreceptors (inhibit NT release): apomorphine reduces dopamine release
9. block autoreceptors (increase NT release): pindolol increases blocks receptor,
increases serotonin release
10. inhibits NT degradation: physostigmine blocks acetylcholinesterase (AChE) so ACh
levels increase, or phenelzine blocks MAO so levels of dopamine, NE, and serotonin
increase in the synapse
11. blocks reuptake of drug: cocaine blocks transporters for dopamine, NE, and
serotonin