Lecture 13: Synaptic Transmissions -> The Details

What two stages in neurotransmitter function are considered presynaptic?

1. Synthesis and Storage
2. Release into the synaptic cleft

How are Classic (small-molecule) NT synthesized and what happens next?

synthesized in cytoplasm, in terminal, from precursor molecules, then loaded into vesicles

Classic (small-molecule) NT examples

* dopamine
* glutamate
* Gaba

How are Peptide NT synthesized and what happens next?

* synthesized by ribosomes, in cell body, directly into vesicles
* THEN transported down the axon, already packaged up

Why are the classic NT’s small?

Because we want them ready and active to use. We use a bunch of them in every single action potential

Why are peptides “expensive”?

They have to be synthesized by ribosomes like proteins so they are much more difficult to produce and take a lot more energy than Classic NT’s

Why are peptides and classic NT’s both considered neurotransmitters?

Because they both sit in vesicles and wait for action potential

What is required for neurotransmitter release?

an action potential in the presynaptic cell is required for neurotransmitter release

What happens when you block voltage gated calcium channels?

Blocking voltage-gated Ca2+ ion channels does block transmitter release!

What is the effect on neurotransmitters when you block Na+ and K+ channels?

neither Na+ influx nor K+ efflux, the major players in the action potential, are necessary for transmitter to be released

What is sufficient for NT release?

Presence of Ca2+ inside the cell

What causes the calcium channels to open and why is it that way?

Calcium channels open when, and only when the cell is depolarized because we have to keep super tight control over it. It controls whether or not neurotransmitters are released so it must be released but it can’t stay in the cell

How is calcium taken out of the cell?

ion exchangers

chelator

binds up a calcium ion so that it can’t interact with anything it would normally interact with inside the cell

What does the use of a calcium chelator prove?

It proves that calcium must interact with things inside the cell in order release neurotransmitters because when the chelator was used, none of the neurotransmitters were released. Calcium is NECESSARY

Can a classic NT or a peptide NT be forced across the lipid blayer?

classic NT

What are SNARES and what do they do?

SNAP receptor proteins that aid in vesicle fusion with the cell membrane for NT release

What are the three major SNAP proteins in complex and what are they anchored to?

* synaptobrevin/VAMP: anchored to vesicle
* syntaxin: anchored to vesicle
* SNAP-25: plasma membrane associated (not transmembrane)

What is synaptotagmin?

calcium sensing SNARE that aids in fusion when calcium enters the cell

What SNARE does calcium bind to and what happens when they bind?

Calcium binds to synaptotagmin and that causes the proteins shape to change

What are the 5 steps of the SNARE process?

1. free SNARES on vesicle and plasma membranes
2. SNARE complexes form vesicle docks
3. Synaptotagmin binds to SNARE complex
4. Entering Ca2+ binds to synaptotagmin, leading to curvature of plasma membranes, which brings the membranes together
5. fusion of membranes leads to exocytosis release of NT

What is synaptic vesicle cycling and what makes it possible?

Horseradish peroxidase allows for The use of and then reuptake of neurotransmitters

What happens to the cell when cytosis occurs?

HRP is taken up into the presynaptic terminals and the endozome

Explain the process of synaptic vesicle cycling…

1. Budding: pieces of cell membrane pinch off of the endosome
2. Docking and Priming: NT’s within vesicles get close to the cell membrane
3. Fusion: vesicles fuse to the cell membrane and release NT’s after the action potential has ocurred
4. Endocytosis: The vesicles or HRP are pinched back into the membrane and released into the endosome to be used again

Is the activation of receptor sites pre or post synaptic?

post synaptic

Each receptor is specific to…

one type of neurotransmitter

No one neurotransmitter is associated with…

a single kind of receptor

What are the two major types of receptors?

ionotropic and matbotropic

ionotropic receptors

receptor and ion channel allows ions to corss the membrane, like voltage gates ion channels (fast)

metabotropic receptors

receptors and proteins that initiate intracellular signaling. Series of events for longterm nudges to the cell

What protein is used for metabotropic ion channels?

G-protein

how does an ionotropic ion channel work?

transmitter binds to the binding site and opens the ion channel immediately, allowing the influx or efflux of ions

How does a metabotropic ion channel work?

NT binds → activates G-protein → opens ion channel or activates effector protein

Why is NT inactivation important?

Because if the NT’s weren’t release quickly, muscles would be constricted for super long periods or static images would be experienced visually

What are the 4 ways neurotransmitter inactivation occurs?

1. diffusion from the synapse
2. enzymatic inactivation
3. neuronal reuptake
4. glial cell cleanup