Lecture 5: Calcium And Synaptic Release

Question 1

What are Quanta (2)

Answer 1

-Neurotransmitter is contained in membrane bound vesicles

-these discrete packages or “quanta” of neurotransmitters

Question 2

Two main forms of release for quanta

Answer 2

-Stimulated by action potential (many, possible dozens or thousands of quanta released)

-Spontaneous (one quanta at a time)

Question 3

v-SNAREs

Answer 3

v-Snares (aka vesicle proteins) are proteins that are part of the active zone during the docking process of neurotransmission. They are inserted into the vesicle, hence the name vesicle proteins

Question 4

t-SNAREs

Answer 4

t-SNAREs (aka membrane proteins) are proteins that are part of the active zone during the docking process of neurotransmission. They are inserted into the terminal membrane, hence the name.

Question 5

6 steps of synaptic release

Answer 5

1. Mobilization
   2.tethering
   3.Docking and priming
2. Superpriming and calcium entry
3. fusion
4. Endocytosis

Question 6

mobilization (6)

Answer 6

First step in synaptic release where:

1. Vesicle is attached to actin filaments by synapsin
2. Entry of Ca++ activates Ca++/CAM dependent kinase in presynaptic terminal
3. The Ca++/CAM kinase phosphorylates synapsins on the vesicle
4. The phosphorylation causes synapsin to release the vesicles, which line up and dock in the active zone
5. vesicle is ready to be tethered

Question 7

tethering (3)

Answer 7

Second step in synaptic release where:

1. the vesicle is reversibly tethered to the active zone by interation of RIM and RAB proteins with voltage gated calcium channels
2. Synaxin is held in an inactive state by Munc18

Question 8

docking and priming (4)

Answer 8

Third step in synaptic release where:

1. Docking occurs when synaptobrevin binds to synatxin and SNAP-25
2. the docking complex is now partially assembled
3. This step is irreversible

Question 9

Superpriming and Ca++ entry (4)

Answer 9

4th step in synaptic release where:

1. vesicle is moved into place directly above the cell membrane
2. Complexin binds to the partially assembled complex, completing it
3. Ca++ ions enter the cell through voltage gated channels due to an action potential being fired, then bind to synaptogamin

Question 10

fusion (5)

Answer 10

The 5th and final step in synaptic release where:

1. Synaptogamin-calcium complex binds to SNARE protiens
2. This displaces complexin, creating a pore in the vesicle through the cell membrane
3. neurotransmitter is released into the cleft
4. NSF and SNAP bind to complex and disassemble it (requires ATP)

Question 11

endocytosis

Answer 11

the REAL final stage of synaptic release where extra cell membrane caused by the fusion of the vesicle to the cell membrane is recycled.

Question 12

two methods of endocytosis

Answer 12

Classical: extra membrane is pinched and removed by clathrin then recycled in the endosome

Kiss and run: Vesicle releases its neurotransmitter then removes itself without the use of clathrin. Can immediately be reused

analogy: Classical model is like taking a beer bottle, melting it down then reforming it. Kiss and run is like taking the same bottle but just rinsing it out before you use it again.