Synaptic Transmission Flashcards

(67 cards)

1
Q

What are the five steps in chemical signaling?

A
  1. Signaling cell
  2. Signal
  3. Receptor
  4. Target molecule
  5. Response
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2
Q

What are the three types of chemical signals?

A
  1. synaptic
  2. paracrine
  3. endocrine
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3
Q

What is the distance between the presynaptic and postsynaptic membranes?

A

~15nm

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4
Q

What is a “fast” chemical synapse?

A

a synapse with a delay between presynaptic depolarization and postsynaptic response of < 1 msec

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5
Q

What are two characteristics of fast chemical synapses?

A
  1. small molecule releasing synapses

2. tight temporal coupling

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6
Q

What are the two main results of treating a squid axon with agents that block Na and K channels and agents that block calcium channels (fig 5.9)?

A
  1. When Na and K channels are blocked, there is still a current through the calcium channels
  2. When calcium channels are blocked, release of nts is inhibited
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7
Q

What are three pieces of evidence that an increase in presynaptic calcium concentration triggers nt release (fig 5.10)?

A
  1. Using fluorescence we can see that presynaptic action potentials cause a rise in calcium concentration
  2. Injecting calcium into the presynaptic terminal causes nt release
  3. Injection of BAPTA into the presynaptic terminal prevents nt release
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8
Q

How is nt release measured?

A

as a depolarization in the postsynaptic terminal

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9
Q

What is BAPTA?

A

a calcium chelater (binds to calcium in selective way)

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10
Q

What is the graphical relationship of calcium concentration to nt release?

A
  • non-linear
  • small increases in concentration results in larger changes of release
  • release = k * [Ca] ^ 4
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11
Q

The relationship between calcium concentration and nt release resulted in what natural occurrence?

A

release is non-linearly dependent on calcium concentration which is why naturally occurring neurotoxins are designed to block calcium channels

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12
Q

How were early defining experiments conducted to find evidence for transmitter release from vesicles (fig 5.5 A)?

A
  • conducted using neuron-muscle synapses
  • motor neuron is stimulated with extracellular electrode and intracellular microelectrode inserted into postsynaptic muscle cell to record electrical responses
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13
Q

What is an EPP and what causes it (fig 5.5 B)?

A
  • end plate potential
  • evoked by stimulation of motor neuron that produces action potential in postsynaptic muscle cell
  • normally above threshold
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14
Q

What are MEPPs and what causes them (fig 5.5 C)?

A
  • spontaneous miniature EPPs

- occur in absence of presynaptic stimulation

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15
Q

What occurs when the neuromuscular junction is bathed in solution of low calcium concentration and the motor neuron is stimulated (fig 5.5 D)?

A

results in EPPs that are about the same size as MEPPs

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16
Q

How large are MEPPs (fig 5.6)?

A
  • all about the same size of 0.4 mV +/- 1 mV
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17
Q

If calcium concentration is increased inside the terminal, how are the MEPPs affected?

A
  • the frequency of the MEPPs increases

- the size/amplitude does not increase

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18
Q

What does the distribution of an EPP amplitude and number of EPPs look like? What does this indicate (fig 5.6)?

A
  • the distribution rises at multiples of 0.4 mV (size of one MEPP)
  • consistent with an action potential evoked EPSP being composed of multiple independent events with a unit size equal to MEPP
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19
Q

How would the graph of EPP amplitude and number of EPPs change if we doubled the extracellular concentration of calcium (fig 5.6)?

A
  • increases probability that fusion will occur by factor of 100,000?
  • controls probability of vesicle fusing
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20
Q

What structural evidence is observed in stimulated terminals?

A
  • postulated vesicles fusing with plasma membrane

- can also see calcium channels

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21
Q

How are synaptic vesicles released and retrieved?

A
  • exocytosis

- endocytosis

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22
Q

What technique was used to observe the structural evidence for synaptic vesicles?

A
  • freeze-fracture electron micrographs at a neuromuscular junction
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23
Q

Why are vesicles practical?

A
  • synchronous
  • osmotic balance
  • large amounts can be released at once (5000 nt per vesicle vs 1/s/pump)
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24
Q

Where do vesicles get released as observed in the structural images?

A

vesicles get released next to rows of calcium channels

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25
What are the three factors that dictate the size of the overall postsynaptic response to a release event?
1. k = "size" of one quantum 2. n = number of available quanta 3. p = probability of release of a quantum (size of EPSP = k * p * n)
26
What is P?
p x n (where p is probability of release and n is number of primed vesicles)
27
What is n?
- number of primed vesicles of action zone | - for multi contacts: number of action zones x number of primed vesicles per zone
28
What is n not?
- n cannot be more than number of docked vesicles but does not mean it is number of docked vesicles - if a vesicle is up against membrane may not actually be ready to release (not "primed")
29
What are the stages in the full fusion model of a vesicle?
1. Budding from endosome 2. Docking 3. Priming 4. Fusion 5. Budding from membrane (endocytosis) 6. Back to join endosome sometimes
30
In the full fusion model, what helps with mobilization?
- synapsin: keeps vesicles tethered - mobilization is caused by phosphorylation of synapsin by protein kinases (calcium/calmodulin-dependent protein kinase type II or CaMKII)
31
In the full fusion model, what helps with priming?
- NSF SNAPs | - SNAREs
32
In the full fusion model, what helps with fusion?
- influx of calcium | - synaptotagmin
33
In the full fusion model, what helps with budding/endocytosis?
- clathrin (forms coat) | - dynamin
34
How does clathrin assist in endocytosis?
- adaptor proteins connect clathrin to membrane | - clathrin triskelia assemble into coat and curve membrane
35
How does dynamin assist in endocytosis?
- dynamin ring forms and pinches off membrane
36
What is the coated vesicle translocated by?
actin filaments
37
What uncoats the vesicle?
- Hsc-70 and auxilin
38
What are the methods of vesicle release?
1. full fusion 2. kiss and run 3. bulk endocytosis
39
What are the proteins (for this course) on the vesicle?
- V-ATPase - SNAP25 - Synatobrevin - Synaptotagmin - Synapsin - VGLUT - Syntaxin
40
What is the function of SNAP25?
- priming - plasma membrane SNARE - forms complex to bring membranes together
41
What is the function of synaptobrevin?
- priming - vesicular SNARE - forms complex to bring membranes together
42
What is the function of synaptotagmin?
- fusing - vesicular calcium-binding protein - binds to SNARE complex - binding of calcium causes cytoplasmic region to insert into plasma membrane to produce membrane curvature that catalyzes membrane fusion
43
What is the function of synapsin?
- keeps vesicles tethered in pool until phosphorylated by protein kinase (CaMK II)
44
What is the function of syntaxin?
- priming - plasma membrane SNARE - forms complex to bring membranes together
45
What three molecules are the core of the SNARE complex?
1. synatobrevin 2. SNAP25 3. Syntaxin
46
What does the SNARE complex do?
SNARE proteins on the vesicle and plasma membranes form complex that brings the two membranes together for docking
47
What is the primed state?
- vesicle and presynaptic membrane are brought together by full zippering of the SNAREs but held in non-fused state
48
Docking involves one more molecule not described in the text, what is it?
Munc18
49
The priming of the pre-fusion complex requires two more molecules not described in the text, what are they?
complexin and ATP
50
What does fusion require and why?
- calcium but not ATP | - calcium binding changes lipid solubility of synatotagmin providing a force to pull membranes together enough to fuse
51
What causes tight channel and vesicle co-localization?
RIM and RIM-BP bind to calcium channels in some synapses
52
From the Sudhoff review, what is required to finish off exocytosis and close fusion pore?
ATP
53
What does familial infantile myasthenia do and how would this affect transmission?
- reduces the vesicle size | - vesicle holds less nt so less transmission
54
What do LEMS do and how does this affect probability of release?
- attacks presynaptic calcium channels | - decreases the probability of release since calcium channels are non-functioning
55
What does congenital myasthenic sydromes result in and how would this affect maintenance of release?
- impaired vesicle recycling - terminal membrane would get larger and there would be less membrane material for new vesicles - rate of release would slow
56
What does latrotoxin result in?
- triggers vesicle fusion
57
What do cognitive disorders result in?
- impair transsynaptic signaling
58
What does botulinum (botox) and tetanus toxins result in?
- affect SNARE proteins involved in vesicle fusion
59
What is observed in a fast synapse?
- large reserve pool of vesicles - "docked" vesicles at active zones - specific active zones
60
What is included in the active zone?
- colocalization of docked vesicles, calcium channels and other proteins that control release
61
Is colocalization always to the same degree?
- no, can have different degrees at different synapses
62
How does differences in colocalization affect calcium influx and release and facilitation of release?
- longer delay between calcium influx and release | - need more calcium for release if less co-localized
63
What do ribbon synapses?
- sustained "asynchronous" release
64
How do the terminals with peptide transmitter differ?
- no active zones | - "vesicles" are larger and called granules or dense core vesicles
65
What does it mean to not have an active zone?
- vesicles not clustered in single spot near membrane | - release in all directions
66
Do synapses release small molecule or neuropeptide?
- can release either or both
67
What is a key difference of peptide release and small molecule release?
- release of peptide typically requires higher frequency stimulation than release of small molecule - needs more calcium to diffuse