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NEUR231 Neurobiology > Neurotransmitters > Flashcards

Neurotransmitters Flashcards

1
Q

What factors define any given NT system?

A
  • NT molecule
  • synthetic machinery
  • packaging
  • reuptake and degradation mechanisms
  • action
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2
Q

What are the 3 criteria for a molecule to be a NT?

A
  1. synthesis & storage in the presynaptic neuron
  2. Released by presynaptic terminal in response to ↑[Ca++]
  3. When applied, elicits/mimics the post-synaptic cell response
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3
Q

What is immunocytochemistry?

A

Process for localising molecules to cells (identifying proteins)

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4
Q

How can we localise classic NT vs neuropeptides?

A

Neuropeptides - we can look for the NT themselves

Classic NTs - can look for their synthesis enzymes

Can only look for proteins

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5
Q

Briefly describe the aim/process of immunohistochemistry

A

Using the immune system to create antibodies against a particular sequence of Amino Acids.
* inject NT candidate
* purify antibodies from the blood
* fix a brain tissue section
* flood with antibodies & they will bind to the AA sequence

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6
Q

What is in situ hybridization?

A

Detect cells when synthesis of a protein/peptide is taking place - by detecting mRNA that codes for that AA sequence

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7
Q

How can NT release be studied?

A

Using a brain slice kept alive in vitro, stimulate synapses, collect & measure released chemicals.

Can also now use optogenetics

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8
Q

How can synaptic mimicry be studied?

A

stimulate the neuron & record the results. Then release a drug & record the results.

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9
Q

What are methods for identifying receptor subtypes?

A
  • Ligand-binding methods - radioligand can show where the drug is binding
  • Molecular analysis - can identify by their molecular/subunit composition
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10
Q

What is Dale’s principle and is it true?

A

A neuron has only one neurotransmitter.
It is true for classic NTs

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11
Q

Describe ACh synthesis in the presynaptic terminal

A

Choline + Acetyl CoA —ChAT–> ACh + CoA

ChAT = choline acetyltransferase [enzyme]

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12
Q

Describe ACh degradation in the synaptic cleft

A

ACh –AChE–> Choline + Acetic acid

AChE = Acetylcholinesterase [enzyme]

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13
Q

Where does Choline come from for ACh synthesis?

A

Choline transporters uptake choline from the synaptic cleft (left there by ACh breakdown by AChE)

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14
Q

Describe the pathway of catecholaminergic NT synthesis & identify the common precursor

A

Common precursor - Tyrosine

Pathway:
Tyrosine
↓
L-Dopa
↓
Dopamine
↓
Norepinephrine
↓
Epinephrine

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15
Q

What are the catecholamine NTs?

A
  • Dopamine
  • Norepinephrine
  • Epinephrine
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16
Q

What determines which NT is synthesised in a catecholaminergic neuron?

A

The enzymes - needs extra enzymes to get further down the pathway between tyrosine & epinephrine

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17
Q

What is the precursor to serotonin?

A

Tryptophan

18
Q

How are the amino acid NTs related?

A

All part of the same synthesis pathway:

Glutamate
↓
Glycine
↓
GABA

19
Q

Which enzyme synthesises GABA from Glutamate?

A

GAD (glutamic acid decarboxylase)

20
Q

Describe ionotropic receptors

A
  • fast transmission
  • sensitive to chemicals/voltage
  • regulate the flow of large currents
  • differentiate between ions (specificity) but not as specific as Na/K channels etc
  • 5 protein subumits (similarity in structure between different ionotropic receptor types)
21
Q

Describe AMPA receptors

A
  • glutamate-gated channels
  • cause EPSPs
  • allows Na+ (inwards) & K+ (outwards) flow
22
Q

Describe NMDA receptors

A
  • glutamate-gated channel
  • causes EPSP
  • Allows Na+ & Ca++ (inwards) & K+ (outwards)
  • has Mg++ gate in place at resting Vm
  • voltage & chemically dependent - requires glutamate binding PLUS strong depolarisation to remove Mg++ gate to open channel
23
Q

What is the general function of GABA-gated and glycine-gated channels?

A

major inhibitory ionotropic receptors

24
Q

Describe a GABA_A receptor

A
  • Cl- channel
  • inhibitory
  • requires GABA to bind to open channel
25
Q

What are the 3 steps in gPCR transmission?

A
  1. NT binds to gPCR
  2. activation of G Protein
  3. Activation of effector systems
26
Q

What are the 3 steps in gPCR transmission?

A
  1. NT binds to gPCR
  2. activation of G Protein
  3. Activation of effector systems
27
Q

What is the basic structure of gPCRs?

A

single polypeptide with 7 transmembrane α-helices

28
Q

List some commonly mentioned gPCRs

A
  • muscarinic receptors (M_1, M_2 etc)
  • GABA_B receptors
  • Dopamine receptors (D1, D2, D3 etc)
  • NE receptors (α1, α2, β1, β2, β3)
  • opiod receptors (µ etc)
29
Q

Where are inactive G proteins found?

A

floating around in the membrane (occasionally bumping into receptors)

30
Q

What are the 3 subunits of a G -protein, and how do they split?

A

α
β
γ

split into Gα and Gβγ functional units

30
Q

What are the 3 subunits of a G -protein, and how do they split?

A

α
β
γ

split into Gα and Gβγ functional units

31
Q

What are the 5 steps of G protein action?

A
  1. G protein subunits together with α bound to GDP (inactive state)
  2. G protein associates with activated gPCR, GDP exchanged for GTP
  3. Gα dissociates from Gβγ, they act on other cellular systems
  4. Gα inactivated when GTP converted to GDP
  5. Gα recombines with Gβγ → reenters inactive state
32
Q

What is an example of a fast, localised G protein response?

A

G protein subunit acting on an ion channel

33
Q

What is a slow G protein response?

A

G protein subunit activating secondary messenger cascades (activation of downstream enzymes)

34
Q

How can different G Proteins have different effects when activated by the same NT?

A

Different G protein types - ie Gs is stimulatory, Gi is inhibitory.

34
Q

How can different G Proteins have different effects when activated by the same NT?

A

Different G protein types - ie Gs is stimulatory, Gi is inhibitory.

35
Q

Compare the activity of α2 and β receptor effects

A

Both activated when NE binds to gPCR.

α2 = Gi receptor → inhibits Adenylyl cyclase
β = Gs receptor → stimulates Adenylyl cyclase

36
Q

Describe the phospholipase C (PLC) second messenger cascade and the singificance of the end result

A
  1. Activated G Protein stimulates PLC
  2. Activated PLC splits PIP2 into DAG & IP3
  3. DAG stimulated Protein Kinase C (PKC)
  4. IP3 stimulates release of Intracellular Ca++

End result: This is another way to ↑[Ca++]

37
Q

What is the function of signal cascades?

A

signal amplification - ie 1 NT binding can then result in many channels being opened later (rather than 1:1 ratio of directly binding ion channel)

38
Q

What is signal divergence?

A

1 NT → lots of different responses (more than 1 receptor type activated)

39
Q

What is signal convergence?

A

Many NT → all eliciting the same response
(different NTs with the same effect)

NEUR231 Neurobiology (11 decks)

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