Week 4: Synaptic Cell Biology Flashcards Preview

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Flashcards in Week 4: Synaptic Cell Biology Deck (14)
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1
Q

Describe the general sequence of NT release in the active zone

A

(1) Synaptic vesicles are held at the active zone via interactions with SNARE proteins
(2) AP depolarizes presyn. membrane, Ca2+ flows in
(3) Ca2+ binds to synaptotagmin, causing a conformational change in the protein that creates a pore in the vesicle and presynaptic membrane, releasing NT into the cleft
(4) The excess intracellular calcium is buffered by the mitochondria and SER to restore homeostasis

2
Q

What are the effects of tetanus and botulinum toxin on NT release?

A

SNAREs are inhibited by tetanus and botulinum toxin so that NT CANNOT BE RELEASED, altering the firing rates of postsynaptic neurons. Tetanus decreases inhibition of alpha motor neuron firing, leading to hyperactivity of the muscle and severe muscular rigidity

3
Q

How are synaptic vesicles recycled?

A

The vesicle fuses with the presynaptic membrane and releases NTs into the cleft. This happens via a clathrin-mediated pathway:
(1) Clathrin assists in pit formation that buds into the cell to form a vesicle

(2) Dynamin cleaves the vesicle from the presynaptic membrane
(3) Clathrin is removed so that SNAREs and other NT transporters can be added to the surface of the vesicle
(4) Modified vesicles are re-loaded with NTs and are ready for the next fusion cycle

4
Q

Where are the enzymes needed for NT synthesis made, and where are they transported to?

A

Enzymes for NT synthesis are made in the RER and are modified in the Golgi. The enzymes are transported anterogradely from the cell body down the axon to the presynaptic terminal. At the presynaptic terminal, NT precursors are actively taken up through the plasma membrane.

5
Q

What is the “exceptional” NT and why is it sooooooo specialllll?

A

Norepinephrine (NE) is made inside of its vesicles

6
Q

How is acetylcholine synthesized?

A

ACh is formed via:

choline + Acetyl-CoA –> ACh, mediated by cholineacetyltransferase (ChAT)

The choline uptake into the presynaptic terminal is the rate-limiting element here

7
Q

What are the two molecules/drugs that can affect AChE, and how do they affect it?

A

Physostigmine is a glaucoma drug that is a reversible AChE inhibitor, increases [ACh] in the synaptic cleft

Sarin is nerve gas, which inhibits AChE, causing ACh to continuously act on the muscle fiber such that the muscle can’t relax

8
Q

How is norepinephrine made?

A

Synthesis begins with tyrosine, which is transported into the cell, and the reactions that occur are:

Tyrosine –> L-DOPA via tyrosine hydroxylase (RATE-LIMITING)

then

L-DOPA –> dopamine via dopamine carboxylase

then, dopamine is transported into the vesicle, and

dopamine –> NE via DA-b-hydroxylase (DBH)

9
Q

How can NE be released, and how can it be degraded?

A

NE is released via Ca2+-mediated NE release

It is degraded by MAO (monoamine oxidase) in the mitochondria, or…

Can diffuse into the circulatory system and be metabolized by MAO and COMT in the liver

10
Q

How is epinephrine made? What step is rate-limiting, and how is it released and recycled?

A

NE leaks out of its vesicles into the cytoplasm, then…

NE –> EPI via PNMT, only in epi neurons and adrenal medulla

(tyrosine hydroxylase is also rate-limiting here)

Release is Ca2+-mediated

Degradation happens via MAO in mitochondria, and MAO/COMT in the liver

11
Q

How is serotonin made? How is it released and recycled? What is the rate-limiting step in formation?

A

Tryptophan is transported into the cell, then…

Tryptophan –> 5-hydroxytryptophan via tryptophan-5-hydroxylase (RATE-LIMITING)

then

5-hydroxytryptophan –> serotonin via aromatic L-amino acid decarboxylase (AADC)

Serotonin release is Ca2+-mediated

It is recycled and taken up into the presynaptic terminal by SERT and loaded into the vesicles, or it is degraded by MAO

12
Q

What are the characteristics of an ionotropic receptor?

A

(1) Ligand-gated ion channel
(2) Ion selective: Na+ entry = depolarization, Cl- entry = hyperpolarization
(3) Fast transmission

13
Q

What are the characteristics of a metabotropic receptor?

A

(1) GCPR
(2) Activate 2nd messenger cascades, open neighboring ion channels, may cause transcriptional changes
(3) Slower, longer-lasting

14
Q

Describe the overall innervation types of motor neurons, sympathetic/paravertebral chain ganglia, prevertebral ganglia, adrenal-stimulating and parasympathetic nerve types

A

(1) Somatic motor neurons have one long, myelinated, cholinergic axon that acts on a nicotinic ion receptor at skeletal muscle NMJs to activate quick contractions
(2) Sympathetic/paravertebral chain ganglia (T1-L2, in the thorax) have short, myelinated, cholinergic preganglionic axons that act on nicotinic receptors. They have longer, unmyelinated, adrenergic postganglionic axons that act on a/B receptors in the blood vessels, glands, and smooth muscle of target tissue
(3) Prevertebral ganglia neurons (T1-L2, in the abdomen) have longer, myelinated, cholinergic preganglionic axons that act on nicotinic receptors AFTER passing through the sympathetic/paravertebral chain ganglia. They have short, unmyelinated, adrenergic postganglionic axons that act on a/B receptors in the blood vessels, glands, and smooth muscle of target tissue.
(4) The adrenal medulla-activating neurons (T1-L2, very low end) have long, direct, myelinated, cholinergic preganglionic neurons. They act directly on the chromaffin cells of the adrenal medulla (it acts like a ganglion), stimulating release of EPI/NE
(5) Parasympathetic neurons in the Cranial Nerve/Sacral regions of the body have long, myelinated, cholinergic preganglionic neurons, and intramural ganglia at which they act on nicotinic receptors. The very short postganglionic neurons act on muscarinic receptors in target tissue.