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09
Advanced Synaptic Transmission II
40
Pharmacology
Undergraduate 2
01/05/2017

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Term
Compare the distance between pre and post-synaptic cell membranes in electrical and chemical synapses
Definition
3.5nm (e)
30-50nm (c)
Term
Does cytoplasmic continuity exist between post and pre synaptic cell membranes in electrical and chemical synapses
Definition
only in electrical
Term
Compare the cytoplasmic components in electrical and chemical synapses
Definition
e: gap junction channels
c: presynaptic active zones and vesicles, postsynaptic receptors
Term
Give the transmission agents in electrical and chemical synapses
Definition
e: ionic current
c: chemical transmitter
Term
Describe the synaptic delay in electrical and chemical synapses
Definition
e: virtually absent
c: at least 0.3ms, 1-5ms
Term
Describe the direction of transmission in electrical and chemical synapses
Definition
e: bidirectional
c: unidirectional
Term
Describe the flexibility in electrical and chemical synapses
Definition
e: none
c: great flexibility due to transmitter and post-synaptic response
Term
Describe the events at an electrical synapse
Definition
1. AP arrives in the presynaptic terminal causing depolarisation
2. voltage gated ca2+ channels are opened by depolarsaiton
3. ca2+ rushed into the terminal at active zones
4. ca2+ trigger NT release
5. ca2+ influx can also influence the shape of the AP
Term
What is the neurotransmitter criteria?
Definition
1. must be synthesised within the synapse
2. must be present in the presynaptic terminal and be released in amounts sufficient to exert its supposed effects of the post-synaptic neurone/effector organ
3. when applied exogenously it must mimic exactly the actions of the endogenously released transmitter
4. must be a specific removal mechanism from its site of action
Term
How are peptide NT synthesised?
Definition
in the cell body using protein manufacturing components (i.e. rER, Golgi apparatus)
Term
How are amine/amino acids NT synthesised?
Definition
in the synaptic terminal using synthesising enzymes that are transported from the cell body
Term
Why are NT synthesised this way?
Definition
so cells can be self-sufficient
Term
Describe small clear vesicles
Definition
40-60nm e.g. GABA, glutamte, dopamine
Term
Describe large dense core vesicles
Definition
90-250nm e.g. neuropeptides
Term
Define co-existance/co-transmission
Definition
a single neurone may synthesis and release more tax one transmitter substance
Term
Describe synaptic vesicles cycling
Definition
1. free vesicles are targeting in active zone
2. vesicles dock in active zone
3. the docked vesicle is primed for exocytosis
4. vesicles undergo fusion and release their contents in response to a rise in [Ca2+]
5. fused vesicle membrane is taken up into the cell by endocytosis
Term
What conc can the micro domain around the active zone can ca2+ reach?
Definition
0.3mM
Term
Name two SNARE proteins
Definition
Synaptobrevin
Synaptotagmin
Term
Describe synaptobrevin
Definition
vesicle bound protein which binds with SNAP-25 on plasma membrane (vesicle priming/docking)
Term
Describe synaptotagmin
Definition
when bound to ca2+ the two c2 domains insert into the membrane and causes the two membranes to fuse by inducing membrane buckling
Term
Describe the vesicle stages
Definition
1. Docking: vesicles move toward and interact with membrane of presynaptic terminal. The distance of these vesicles from a Ca2+ channel cluster ranges from 30-300μm (mean is around 100μm).
2. Priming: vesicles become competent for fusion-pore opening ;all the molecular rearrangements that take place after initial docking of a synaptic vesicle but before exocytosis have occurred.
3. Fusion-pore opening: Ca2+ induced; once Ca2+ has entered the presynaptic cell, the neurotransmitter will be released. This is related to fast transmitter release.
Term
What are the functions of vesicle proteins?
Definition
1. Restraint of vesicles: interaction with the cytoskeleton to move vesicles over a short distance.
2. Recruitment of neurotransmitter vesicles from the reserve pool to the releasable pool.
3. Docking of vesicles: attachment to the presynaptic plasma membrane.
4. Priming of vesicles: preparation for release.
5. Rapid fusion and exocytosis upon intracellular Ca2+ increase.
6. Endocytosis: recycling and reuptake into presynaptic cell.
Term
Whats a V-snare?
Definition
synaptobrevin (vesicle)
are incorporated into the membranes of transport vesicles during budding.
Term
Whats a T-snare?
Definition
SNAP-25, syntaxin (target)
are located in the membranes of target membranes.
Term
How does ca2+ binding allow synaptotagmin to initiate formation of SNARE complex?
Definition
a) calcium binding allows synaptotagmin to initiate formation of SNARE complex
b) SNARE complex forms with snaptotagmin, calcium increase causes membrane juxtaposition and allows fusion
Term
Vesicles in the nerve terminal are grouped into three pools, which are distinguished by their function and position in the nerve terminal - what are they?
Definition
1. Readily releasable pool
2. Recycling pool
3. Reserve pool
Term
Describe the readily releasable pool
Definition
docked to the cell membrane, making these the first group of vesicles to be released on stimulation. The readily releasable pool is small and is quickly exhausted.
Term
Describe the recycling pool
Definition
proximate to the cell membrane, and tend to be cycled at moderate stimulation, so that the rate of vesicle release is the same as, or lower than, the rate of vesicle formation. This pool is larger than the readily releasable pool, but it takes longer to become mobilised.
Term
Describe the reserve pool
Definition
constitutes the vast majority of vesicles in the nerve terminal, but it is not clear that vesicles in this pool are released under normal conditions. Under experimental conditions, this pool is mobilised by intense stimulation, and might occur only once the other two pools are exhausted.
Term
What toxins affect NT release?
Definition
botulinum and tetanus
both produce the enzyme zinc endoprotease. This enzyme catalyses the hydrolysis of peptide bonds, which means it has the ability to cleave the SNARE proteins actively involved in vesicle fusion.
Term
What proteins are affected by toxins?
Definition
Synaptobrevin: cleaved by both C. botulinum and C. tetani.

SNAP-25: cleaved by C. botulinum.

Syntaxin: cleaved by C. botulinum.
Term
Describe NT release
Definition
1. vesicles cluster at the active zone waiting to be released by the synaptic neurone
2. vesicles fuse with post-synaptic membrane and release NT into cleft
Term
How can a NT be removed?
Definition
1. reuptake of NT into terminal
2. diffusion of NT
3. enzymatic breakdown of NT
4. binding of NT to postsynaptic receptors/presynaptic auto receptors
Term
What do vesicle transporters do?
Definition
concentrate NT into vesicles
several Its may utilise a single type of transporter
low level specificity
Term
What do membrane transporters do?
Definition
responsible for reuptake of NT from synaptic cleft
high levels of specificity needed
Term
How does a NT enter a vesicle?
Definition
energy is released demo breakdown of ATP into ADP on veils surface using ATPase
proton produced is transported into vesicles
proton dependent 'antiporters' transport NTs
Term
Describe membrane transporters
Definition
sequester NTs
maintain ion gradients
provide nutrients
sodium dependent sympoters
active trnapsort concentrates NT in cytoplasm
Term
How many sodiums are swapped for
choline
GABA
Glutamate
Definition
1
2
3
Term
Define disinhibiton
Definition
the arrangement of inhibitory and excitatory cells in a circuit that generates excitation by the transient inhibitor of a tonically active neurone
Term
Draw and explain disinhibition diagram
Definition
see notes
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