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Neurology > GABA (FS - Week 2) > Flashcards

GABA (FS - Week 2) Flashcards

1
Q

Name 3 neurotransmitter criteria

A
  1. molecule must be synthesised and stored in presynaptic neuron
  2. once synthesised NT is taken up into vesicles and released from the presynaptic axon terminal upon stimulation
  3. molecules must produce a response in postsynaptic cells
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2
Q

What type of neurotransmitter is GABA?

A

major inhibitory in the CNS

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3
Q

What is GABA short for?

A

Gamma-aminobutyric acid

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4
Q

Name the steps of GABA synthesis

A

Glucose > Glutamate > *GABA

  • by the enzyme Glutamate decarboxylase (GAD) and pyridoxal phosphate
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5
Q

Name the steps of GABA being transferred into vesicles

A

GABA >* Vesicles

  • by the enzyme VIAAT (vesicular inhibitory amino acid transporters)
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6
Q

What type of vesicles is GABA stored in?

A

Oval

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7
Q

What type of vesicles is Glutamate stored in?

A

Round

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8
Q

What is pyridoxal phosphate derived from?

A

vitamin B6

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9
Q

The absence of this substance can lead to diminished amounts of GABA and as a result can cause seizures. Name that substance

A

vitamin B6

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10
Q

What is the transporter that reuptakes GABA

A

GABA re-uptake transporters (GATs)

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11
Q

Which enzyme is responsible for turning glutamate into GABA?

A

Glutamate decarboxylase (GAD)

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12
Q

Which GABA re-uptake transporter (GAT) sub-type is predominantly expressed on neurons?

A

GAT-1

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13
Q

Which GABA re-uptake transporter (GAT) sub-type is predominantly expressed on glial cells?

A

GAT-3

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14
Q

Which subunit interface comprises the GABAa receptor binding site for GABA?

A

alpha and beta

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15
Q

The GABAb receptor permits the efflux of which type of ion?

A

K+

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16
Q

Name the steps in the degradation of GABA

A

GABA > *Succinic semialdehyde > **succinic acid

  • by the enzyme GABA transaminase (GABA-T)

** by the enzyme succinic semialdehyde dehydrogenase (SSADH)

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17
Q

What enzyme degrades GABA to Succinic semialdehyde?

A

GABA transaminase (GABA-T)

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18
Q

Name the two families of neurotransmitter receptors

A
  1. GPCRs (G-protein coupled receptors)

2. LGICs (Ligand-gated ion channels)

19
Q

Explain the mechanism of action of ligand-gated ion channels.

A
  1. neurotransmitter binds and allow channel to open
  2. ions pass through the channel
  3. this increases or decreases the chance of an action potential firing - this depends on the type of neurotransmitter that binds
20
Q

Explain the mechanism of action of GPCRs

A
  1. Neurotransmitter binds and activates molecular switches called G-proteins (comprised of a,B,Y subunits)
  2. these subunits dissociate and interact with ion channels or bind to other effector proteins e.g. enzymes
  3. this activates a secondary messenger pathway that opens or closes ion channels
21
Q

What type of receptor is GABAa?

A

ionotropic/Ligand-gated ion channel

22
Q

What type of receptor is GABAb?

A

Metabotropic/GPCR

23
Q

What type of receptor is GABAc? Why is it different?

A

ionotropic/LGIC

it has a similar structure to GABAa but is insensitive to drugs that act at GABAa

24
Q

The GABAa receptor permits the influx of which ion?

A

Cl-

25
Q

Describe the structure and function of the GABAa receptor

A
  • hetro pentameric receptor with 5 subunits
  • most common complement of subunits is 2a, 2B, Y
  • it is a ligand gated ion channel
  • it allows the influx of Cl- ions
  • it increase neuronal inhibitory drive
26
Q

What subunit/s do Benzodiazepines bind to on the GABAa receptor? What is the therapeutic drug target of these drugs?

A

alpha and gamma

Anxiety - increases GABAergic neurotransmission to reduce anxiety symptoms

27
Q

What subunit/s does GABA bind to on the GABAa receptor?

A

alpha and beta

28
Q

What subunit/s does picrotoxin bind to?

A

it blocks the GABA receptor pore

29
Q

What subunit/s do allosteric modulators e.g barbiturates bind to?

A

beta and gamma

30
Q

How many transmembrane domains does the GABAb receptor have?

A

7

31
Q

The GABAb receptor is a dimer - what subunits is it comprised of?

A

GABAb1 and GABAb2

32
Q

Describe the mechanism of action of the GABAb receptor

A
  1. neurotransmitter binds
  2. activates Gi/o G-protein which dissociates from GABAb receptor
  3. this activates secondary messenger system:
    - inhibits adenylate cyclase = decrease in cAMP
    - activates K+ channels = efflux of K+ & blocks Ca2+ channels = hyperpolarisation
33
Q

What is depolarisation?

A

displacing the membrane potential towards a more positive value in order to fire an action potential

34
Q

What is hyperpolarisation?

A

displacing the membrane potential towards a more negative value in this inhibits the firing of an action potential by increasing the stimulus needed to fire an action potential

35
Q

During hyperpolarisation - what ions are involved?

A

influx of Cl-

efflux of K+

36
Q

What cells in the cerebellum are GABAergic neurons?

A

Purkinje cells

37
Q

Why does the balance of GABA and Glutamate need to be regulated?

A

to ensure normal brain function so there isn’t an imbalance of excitatory or inhibitory neurotransmitter

38
Q

What happens when there is too much Glutamate?

A

Epileptic seizures - this will stimulate GABA enhancement.

39
Q

Name 5 types of drugs that act to enhance GABAergic neurotransmission

A
  1. GABAa receptor enhancers
  2. GAT blockers
  3. GABA Transaminase inhibitors
  4. GAD modulators
  5. Prodrugs
40
Q

What types of drugs are Barbiturates and Benzodiazepines? How do they increase GABAergic neurotransmission?

A

GABAa receptor enhancers

they act as positive allosteric modulators of GABAa receptor

41
Q

What types of drug is Tiagabine?

How does it increase GABAergic neurotransmission?

A

GAT blocker

inhibits the reuptake of GABA into presynaptic neuron which increases amount of GABA in synapse

42
Q

What types of drug is Vigabatrine?

How does it increase GABAergic neurotransmission?

A

GABA transaminase inhibitor

inhibits transaminase which inhibits GABA degradation

43
Q

What types of drugs are Gabapentin and Valproate? How do they increase GABAergic neurotransmission?

A

GAD modulators

increase GAD enzyme activity = more conversion of Glutamate to GABA

44
Q

What types of drug is Progabide?

How does it increase GABAergic neurotransmission?

A

Prodrug

it is an inactive precursor that can be metabolised by the body into GABA to increase availability

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