Lecture 6 Flashcards

1
Q

What are three classes of neurotransmitters?

A

Amino acids, amines, peptides

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2
Q

What are the different types of neurotransmitters?

A
  • Only one neurotransmitter (Dale’s principle)
  • Co-transmitters: two or more transmitters released from one nerve terminal
  • Nomenclature (-ergic): cholinergic, noradrenergic, GABAergic, etc.
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3
Q

How are different particular transmitter systems defined?

A

By molecule, synthetic machinery, packaging, reuptake/degradation, and action

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4
Q

What are the 3 study criteria for establishing a neurotransmitter?

A

1) Synthesis and storage in presynaptic neuron
2) Released by presynaptic axon terminal
3) When applied, mimics postsynaptic cell response produced by release of neurotransmitter from the presynaptic neuron

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5
Q

What are 3 ways we study neurotransmitter systems?

A

1) Localizing transmitters and transmitter-synthesizing enzymes
2) In situ hybridization: localize synthesis of protein or peptide to a cell to detect mRNA
3) Immunocytochemistry: localize molecules to cells

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6
Q

What is the qualifying condition for studying synaptic mimicry?

A

Molecules evokes same response as neurotransmitters

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7
Q

What is microiontophoresis?

A

technique in which drugs can be ejected in very small amounts to assess postsynaptic actions

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8
Q

What are microelectrodes?

A

measures effects on membrane potential

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9
Q

What receptors are used in molecular analysis?

A

1) Transmitter-gated ion channels (ionotropic receptors)
- GABA (a) receptors
- 4-5 subunits, each made with various combos of subunit polypeptides
2) G-protein-coupled receptors (metabotropic receptors)
- GABA (b) receptors
- 7-transmembrane signaling molecules

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10
Q

What was the first identified neurotransmitter? Where is it typically found?

A

ACh (Acetylcholine) - vertebrate neuromuscular junctions

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11
Q

What happens in Cholinergic Neurons?

A

ACh synthesis and degradation

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12
Q

What enzyme is needed for ACh synthesis?

A

ChAT enzyme (Choline acetyltransferase)

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13
Q

What enzyme mediates ACh degradation?

A

acetylcholinesterase (AChE)

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14
Q

What are catecholaminergic neurons involved in?

A

movement, mood, attention, and visceral function

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15
Q

What is the precursor for dopamine, norepinephrine, epinephrine?

A

Tyrosine! They all contain catechol group

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16
Q

What enzymes are involved in making catecholamines?

A

Tyrosine hydroxylase, Dopa decarboxylase, Dopamine Beta-hydroxylase, phentolamine N-methyltransferase

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17
Q

What are serotonergic neurons derived from?

A

Tryptophan

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18
Q

What do serotonergic neurons regulate?

A

mood, emotional behavior, sleep

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19
Q

What can people take to help with serotonergic neurons?

A

SSRIs - Selective serotonin reuptake inhibitors

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20
Q

How is serotonin made?

A

2 steps from tryptophan with tryptophan hydroxylase and 5-HTP decarboxylase

21
Q

What are examples of amine acidergic neurons?

A

Glutamate - major excitatory CNS neurotransmitter
CABA - major inhibitory CNS neurotransmitter
Glycine

22
Q

What is glutamic acid decarboxylase (GAD)?

A

Key enzyme in GABA synthesis & good marker for GABAergic neurons

23
Q

Why are GABAergic neurons important?

A

major source of synaptic inhibition in the CNS

24
Q

What transporters are needed to load GABA and Glutamate into synaptic vesicles?

A

Vesicular GABA transporter (vGAT) and Vesicular glutamate transporter (vGlut)

25
Q

What are examples of Ach receptors? What goes in and comes out in each?

A

Nicotinic receptor = + nicotine, - curare
Muscarinic receptor = + muscarine, - atropine
Both have + ACh in

26
Q

What are examples of glutamate receptors? What are their respective agonists?

A

AMPA receptor: AMPA
NMDA receptor: NMDA
Kainate receptor: Kainate

27
Q

What are the benefits of neurotransmitter-gated ion channels?

A
  • Fast synaptic transmission
  • Can turn chemical signal into electrical signal
  • Ion selective
28
Q

What is the basic structure of transmitter-gated channels?

A

Tetramer: 4 protein subunits form a pore
Pentamer: 5 protein subunits form a pore

29
Q

What are AMPA receptors permeable to?

A

Na+ and K+

30
Q

What are NMDA receptors permeable to?

A

Na+ and K+ and Ca++

31
Q

How does the voltage-dependent NMDA channels work?

A
  • Require glutamate binding and membrane depolarization to open channel
  • Blocked by Mg++ ions at negative resting membrane potentials
  • Removal of Mg++ block happens when membrane depolarizes
32
Q

What does GABA-gated mediate?

A

Most synaptic inhibition in CNS

33
Q

What do glycine-gated channels mediate?

A

non-GABA synaptic inhibition

34
Q

What do amino acid-gated channels bind?

A

ethanol, benzodiazepines, barbiturates

35
Q

What are other neurotransmitter systems?

A

endocannabinoids, retrograde messengers
- act on presynaptic g-protein coupled receptor cannabinoid receptors

36
Q

What are the basic structures of g-protein couples receptors (GPCRs)?

A

Single polypeptide with 7 membrane-spanning alpha-helices

37
Q

What are the 3 steps in transmission?

A
  • Binding of the neurotransmitter to the receptor protein
  • Activation of G-proteins
  • Activation of Effector systems
38
Q

What are the inactive g-protein subunits?

A

alpha bound to GDP, beta, gamma

39
Q

When is GPCR active?

A

G-protein complex activated by receptor and exchanges GDP for GTP on G-alpha

40
Q

How does GPCR activate, inactivate, and start over?

A

Alpha dissociates from beta-gamma and GDP swaps with GTP
G-alpha is inactivated by hydrolysis of GTP to GDP
Alpha and beta-gamma recombine to start over

41
Q

What is the shortcut pathway for GPCR?

A

From receptor to G-protein to ion channel
- super fast and localized

42
Q

What is the second messenger cascade pathway?

A

g protein couples with neurotransmitter with downstream enzyme activation

43
Q

How does push-pull signaling work?

A
  • different g-proteins stimulate or inhibit adenylyl cyclase)
  • Gi : adenylyl cyclase inhibitory G-alpha protein
  • Gs: adenylyl cyclase stimulatory G-alpha protein
44
Q

Explain the IP3 and DAG signaling cascade.

A

1) G-protein activation of phospholipase C (PLC)
2) Lipase that hydrolzes phosphatidylinositol 4, 5-bisphospahete (PIP2) to make DAG and IP3
- IP3 binding to IP3 receptors at the ER to release calcium stores
- DAG helps activate protein kinase C
3) Activated different effectors

45
Q

What’s the benefit of GPCR signaling cascades?

A

Powerful signal amplification

46
Q

What is a common regulator mechanism of target proteins?

A

Phosphorylation and dephosphorylation
- changes conformation and biological activity

47
Q

What is the difference between divergence and convergence?

A

Divergence: one transmitter activates more than one receptor subtype
Convergence: different transmitters converge to affect the same effector system

48
Q

Which creates a greater postsynaptic response: divergence or convergence?

A

divergence