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Physiology 2 > Neuro: Neurotransmitters Systems II: GABA & Glycine > Flashcards

Neuro: Neurotransmitters Systems II: GABA & Glycine Flashcards

1
Q

What type of neurotransmitter are GABA and glycine?

A

Inhibitory neurotransmitters - cause membrane potential hyperpolarisation

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2
Q

What is hyperpolarisation?

A

Displacement of a membrane potential towards a more negative value

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3
Q

What are the two ways that hyperpolarisation of a membrane can occur?

A
  • Influx of negatively charged ions into the cell e.g. Cl-
  • Efflux of K+ ions out of the cell
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4
Q

How is GABA synthesised within the pre-synaptic neurone?

A
  • GABA is produced from glutamate via the enzyme glutamate decarboxylase (GAD)
  • Glutamate decarboxylase requires a cofactor called pyridoxal phosphate
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5
Q

How is GABA stored within the pre-synaptic neurone once it’s synthesised?

A

GABA is transported into synaptic vesicles via the vesicular inhibitory amino acid transporter (VIAAT)

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6
Q

What is the difference in the synaptic vesicles that GABA and glutamate are stored in?

A
  • Glutamate stored in round synaptic vesicles
  • GABA stored in oval synaptic vesicles
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7
Q

What are the different types of GABA receptor?

A
  • GABAA receptor
  • GABAB receptor
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8
Q

What type of receptor is the GABAA receptor and how does it cause hyperpolarisation?

A
  • GABAA receptor is a ligand-gated Cl- channel
  • It causes hyperpolarisation by causing the influx of Cl- into the cell when activated
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9
Q

What are the different subunits/subtypes that can make up the GABAA receptor?

A
  • α1-α6
  • β1-β3
  • γ1-γ3
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10
Q

What is the most common configuration of subunits of the GABAA receptor?

A
  • Pentameric structure
  • 2α 2β γ most common configuration
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11
Q

What is the name of the transporter responsible for the re-uptake of GABA back into the pre-synaptic neurone?

A

GABA reuptake transporter (GAT)

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12
Q

What are the different binding sites present on the GABAA receptor?

A
  • GABA binding sites - between α and β subunits
  • Benzodiazepine binding site
  • Channel blocker binding sites
  • Channel modulator binding sites
  • Allosteric modulator binding sites
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13
Q

What type of receptor is the GABAB receptor?

A

G-protein coupled receptor

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14
Q

What are the different subunits of the GABAB receptor?

A
  • GABAB1
  • GABAB2
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15
Q

What are the different configurations of the subunits of GABAB receptors?

A
  • Form dimers
  • Can be homomers - e.g. GABAB1 and GABAB1
  • Can heteromers - e.g. GABAB1 and GABAB2
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16
Q

What type of G protein is the GABAB receptor coupled to?

A

Gi/o

17
Q

How does activation of the GABAB receptor cause hyperpolarisation?

A
  • Activation of GABAB receptor results in K+ efflux out of the cell
  • Also causes inactivation of the voltage-gated Ca2+ channel preventing Ca2+ influx into the cell
18
Q

Both neurons and glial cells have GABA reuptake transporters (GAT), what type of GAT do the glial cells and neurons have?

A
  • Glial cells have GAT-3
  • Neurons have GAT-1
19
Q

Explain how is GABA degraded

A
  • GABA is converted into Succinic semialdehyde by GABA transaminase (GABA-T)
  • Succinic semialdehyde is then converted into succinic acid by Succinic semialdehyde dehydrogenase (SSADH)
20
Q

How is the brain able to control it’s level of excitation?

A

Brain is able to convert Glutamate into GABA via Glutamate decarboxylase (and pyridoxal phosphate) to keep a constant excitatory-inhibitory balance

21
Q

What is epilepsy?

A

Brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons

22
Q

What are the different types drugs that can treat epilepsy via increasing inhibition via GABA?

A
  • GABAA receptor enhancers e.g. progesterone
  • GABA reuptake transporter (GAT) blockers
  • GABA-transaminase inhibitors
  • Glutamate decarboxylase (GAD) modulators
  • Progabide - precusor to GABA
23
Q

What is anxiety?

A

Feeling of unease which can range from mild to severe

24
Q

What are anxiolytics and what receptor do they work on?

A
  • Anxiolytics are drugs used to reduce anxiety
  • They bind to/work on the GABAA receptor
25
Q

How is Glycine synthesised in the pre-synaptic neurone?

A
  • 3-phosphoglycerate is converted into serine by glycolysis
  • Serine is then converted into Glycine via serine-hydroxymethyl-transferase
26
Q

How is glycine stored within the pre-synaptic neurone?

A

Glycine is transported into vesicles by the vesicular inhibitory amino acid transporter (VIAAT)

27
Q

What type of receptor is the glycine receptor and how does it cause hyperpolarisation?

A
  • Glycine receptor is a ligand-gated Cl- channel
  • Causes hyperpolarisation by causing influx of Cl- when activated
28
Q

What are the different subunits of the glycine receptor?

A
  • α1-α4
  • β
29
Q

What is the most common configuration of the Glycine receptor subunits?

A
  • Pentameric structure
  • Most common configurations are 3α1 and 2β or 4α1 and a β
30
Q

What is the name of the transporter responsible for the re-uptake of glycine back into the pre-synaptic neurone?

A

Glycine reuptake transporter (GlyT)

31
Q

Just like the GABA reuptake transporter (GAT) both Glial cells and neurones have Glycine reuptake transporters, what type of glycine reuptake transporter do they each have?

A
  • Glial cells - GlyT-1
  • Neurones - GlyT-2
32
Q

Explain how glycine is degraded

A

Glycine is converted into serine via the enzyme serine hydroxymethyl-transferase

33
Q

What is hyperekplexia?

A

Rare disorder characterised by hypertonia (increased muscle tone) and an exaggerated startle response

34
Q

What role does glycine have in the development of hyperekplexia?

A
  • Gene mutations in glycine receptors or transporters can disrupt glycinergic neurotransmission
  • This can lead to hyperexcitability as inhibition via glycine neurones can’t happen
  • This hyperexcitability leads to symptoms of hyperekplexia

Physiology 2 (29 decks)

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