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► Med - Year 1 > Neurotransmitters 2 > Flashcards

Neurotransmitters 2 Flashcards

1
Q

The major inhibitory transmitter in CNS

A

GABA (gamma-aminobutyric acid)

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2
Q

As many as ___ of the synapses in brain use GABA, most common in ______

A

1/3, local circuit interneurons (talk to each other by electrical and chemical synapses)

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3
Q

GABA is derived from ____ and is/is not used in protein synthesis

A

Glucose metabolism, is not used in protein synthesis

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4
Q

Like Glutamate, levels of GABA are high/low

A

High (mM)

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5
Q

Glutamate is converted into GABA in one step via this enzyme

A

Glutamic acid decarboxylase (GAD)

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6
Q

GAD requires what for activity?

A

Pyridoxal phosphate (VB6 active form)

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7
Q

How can VB6 deficiency cause seizures?

A

Vitamin B6 needed for GAD activity, need GAD to make GABA neurotransmitter

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8
Q

When GABA action is terminated, it has these two fates using which transporter?

A
  1. Uptake into presynaptic terminal to be reused
  2. Uptake by glial cell where GABA is metabolized/degraded (different than w. uptake of glutamate, which gets converted to glutamine and then reused by presynaptic cell)

Both use GAT (GABA transporter)- family of 4 GATs

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9
Q

GABA uses what transporter to get concentrated in SVs

A

VIATT

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10
Q

Unlike Glutamate, GABA has this one major job

A

Intercellular signaling

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11
Q

During development, GABA is excitatory/inhibitory

A

excitatory

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12
Q

During development, intracellular Cl- is (higher/lower), and reversal potential for Cl- is (above/below) threshold. GABA is inhibitory/excitatory, and opens ion channels, causing (hyper/depolarization)

A

intracellular is higher (35 mM)
reversal potential is above threshold (-30 mV)
GABA is excitatory
Ion channel opens, Cl- leaves cell, causing depolarization
triggers Ca2+ influx and signaling

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13
Q

In adult, intracellular Cl- is (higher/lower), reverse potential for Cl- is (above/below) threshold, GABA is inhibitory/excitatory and opens ion channels, causing (hyper/depolarization)

A 
Intracellular Cl- is lower (5mM)
reverse potential is below threshold (-70)
GABA is inhibitory
Opens ion channels and Cl- enter cells
Causes hyperpolarization
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14
Q

GABA is synthesized by these two GAD genes

A

GAD67, GAD65

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15
Q

This GAD gene is rate limiting; influences cellular GABA content in dosage-dependent manner; turns over rapidly

A

GAD67

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16
Q

Major inhibitory transmitter in the spinal cord

A

Glycine

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17
Q

Glycine is made from ___ by mitochondrial isoform of this enzyme

A

Serine; Ser hydroxymethyltransferase (Ser HMT)

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18
Q

Like GABA, Gly uses this transporter to get into SVs

A

VIATT

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19
Q

Fate of glycine after taken up by astrocyte

A

degradation

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20
Q

after release, Gly gets taken up by astrocytes or presynaptic vesicles by these two transporters

A

GlyT1 (astrocytes)

GlyT2 (pre-synaptic)

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21
Q

This makes either GlyT1 or GlyT2 lethal

A

KO

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22
Q

Three important catecholamines

A

Epi, Norepi, dopa (all from tyrosine)

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23
Q

Catecholamines are made by what percentage of neurons in brain

A
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24
Q

almost all neurons are close to a terminal releasing

A

catecholamines (small number of cell bodies, but lots of processes that go pretty much all over brain)

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25
Q

Main base for catecholamines

A

Substantia nigra and ventral tegmental area

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26
Q

Rate limiting step in catecholamine biosynthesis. What does it require?

A

Tyrosine –*–> Dihydroxyphenylalanine (DOPA)
*tyrosine hydroxylase
requires Fe and O2

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27
Q

Aromatic amino acid enzyme that is not rate limiting; non specific, fast, needs pyridoxal phosphate

A

DOPA —*—> Dopamine (dopamine neurons stop here)

*DOPA decarboxylase (also called aromatic amino acid decarboxylase, AAAD)

28
Q

List steps for catecholamine biosynthesis starting from Dopamine. List the two enzymes. Where do sympathetic neurons mostly stop?

A

Dopamine —> Norepinephrine (dopamine beta-monooxygenase [ Sympathetic neurons stop here]

Norepinephrine —> Epinephrine (PNMT, uses S-adenosylmethioine to make it)

29
Q

Where is Dopamine beta-monooxygenase located?

A

Inside vesicles (dopa -> norepi)

30
Q

This transporter transports dopa, norepi, and epi uphill into vesicles as protons leave

A

VMATs (vesicular monoamine transporters)

31
Q

Adrenal chromaffin cells and a few CNS neurons make this catecholamine

A

Epinephrine

32
Q

Catecholamine storage

A

small dense core vesicles

33
Q

In converting dopamine to norepi, dopamine beta-monooxygenase (dopa beta hydroxylase) has some interesting requirements. List the 3

A

O2, vitamin C, copper

34
Q

Norepi influences these 4 behaviors

A

sleep, wakefulness, attention, feeding behavior

35
Q

Which three enzymes in synthesis of catecholamines are cytosolic?

A
  1. TH (tyrosine hydoxylase)
  2. AAAD
  3. PMNT
36
Q

This transporter is more neuroendocrine in all cells of adrenal medulla

A

VMAT1

37
Q

This transporter is in peripheral, central, and enteric neurons

A

VMAT2

38
Q

Explain why vesicular stores of catecholamines are dynamic

A

VMAT-mediated uptake is countered by leakage of catecholamines back into pre-synaptic cytosol

39
Q

What is a key step in catecholamine signaling?

A

Reuptake; most of catechs released from a nerve terminal is retrieved; ends transmitter action and allows re-use

40
Q

What does cocaine inhibit?

A

Dopamine transporter (DAT)

41
Q

What upregulates DAT but not VMAT1 or 2?

A

Chronic cocaine

42
Q

Synaptic vesicles that contain catecholamines can be small or large, and they are electron dense. List 5 important things they contain

A
  1. Chromagranin A (protein)
  2. D beta M (DBM)
  3. Bioactive peptides
  4. ATP
  5. Ascorbate

*catecholamine storage have many of the same proteins as ACh vesicles *

43
Q

pH inside vesicle

A

5.5

44
Q

Where does breakdown/metabolism of catecholamines occur?

A

Primarily in neuron that made it

45
Q

In the process of removal, this enzyme oxidizes dopa, NE and epi, forming short-lived catecholaldeydes

A

Monoamine oxidase (MAO)

46
Q

What makes supply of catecholamines available to MAO?

A

Vesicular uptake and leakage

47
Q

Plasma membrane catecholamine transporters and vesicular catecholamine transporters are (related/unrelated)

A

unrelated

48
Q

Histamine is made by neurons in this region of the brain

A

Hypothalamus (with projections to spinal cord and most brain regions)

49
Q

mediates arousal and attention

A

histamine

50
Q

Serotonin is used in groups of neurons in what areas of brain

A

Neurons in pons and upper brainstem with widespread projections to forebrain

51
Q

What does serotonin affect?

A

Sleep and wakefulness

52
Q

Serotonin is made from

A

tryptophan (dietary requirement)

53
Q

How does Serotonin synthesis resemble that of catecholamines? List 5.

A
  1. Hydroxylase, rate limiting step
  2. AAAD
  3. molecular O2
  4. VMAT transport
  5. Cytosolic enzyme
54
Q

Inhibitory local circuit neurons use what type of peptides?

A

Opiate peptides

55
Q

This is a serotonin (5-HT) specific plasma membrane transporter, homologous to DAT and NET

A

SERT

56
Q

Every gene encoding a neuropeptide encodes a prepropeptide with an ___-terminal signal sequence

A

NH2-terimnal

57
Q

What guides ribosomes translating mRNA encoding pre-proneuropeptide to membranes of ER?

A

Signal sequences

58
Q

You need this type of enzyme to release active peptides from inactive precuror: they recognize specific cleavage sites

A

Endoproteases

59
Q

All of the pieces of the precursor are usually secrete (together/separately)

A

Together

60
Q

Synthesis of neuropeptides occurs here

A

Nerve terminal

61
Q

Is there re uptake of peptides?

A

No; once released, no-reuptake

62
Q

Do many synapses use both small molecule and peptide transmitters?

A

YES!

63
Q

Release of small molecule neurotransmitters in small clear core vesicles (SSVs) occur with (high/low) frequency stimulation (widespread/localized) increase in Ca2+

A

Low frequency stimulation, and localized increase in Ca2+

64
Q

Release of peptides from large dense core vesicles (LDCVs) require what type of frequency stimulation and what type of increased in Ca2+?

A

Higher frequency stimulation, more widespread increase in Ca2+

65
Q

major inhibitory transmitter in spinal cord

A

glycine

► Med - Year 1 (48 decks)

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