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Ageing block > Glutamate & GABA > Flashcards

Glutamate & GABA Flashcards

1
Q

What type of neurotransmitter is glutamate?

A

Excitatory

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2
Q

What type of neurotransmitter is GABA?

A

Inhibitory

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3
Q

Do you take up neurotransmitters in your diet?

A

No, you take up precursors then the brain makes the neurotransmitter wherever it is needed

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4
Q

What type of signalling occurs from the presynaptic terminal- synaptic cleft- Post synaptic cell?

A
  • Electrical impulse occurs across the presynaptic terminal
  • Chemical signalling occurs across the synaptic cleft
  • Electrical impulse occurs across the post synpatic cell
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5
Q

Describe the 2S,3R,2D (SSRRRDD) system

A 
S: Synthesis
S:Storage
R:Release
R:Receptors 
R:Reuptake
D:Degradation
D:Drugs& disease
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6
Q

Outline the characteristics of glutamate

A
  • Amino acid
  • Widely distributed in the CNS 70% of all synapses
  • Very little in the PNS
  • The most important excitatory NT in the CNS
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7
Q

Outline the synthesis of glutamate

A

In the neurone Glutamine is converted to glutamate via the enzyme glutaminase

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8
Q

How and where is glutamate converted into glutamine

A

Glutamate is converted into glutamine via the enzyme glutamine synthase in the glia

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9
Q

How are glutamate and GABA connected

A

Glutamate is converted into alpha-ocoglutarate using the enzyme transaminase
-Alpha-oxoglutarate is converted into glutamate using GABA transaminase

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10
Q

Outline the storage of Glutamate and explain how this is made possible

A
  • Packaged into vesicles
  • This is made possible as the vesicle contains a vesicle glutamate transporter (3 different types)
  • The glutamate is transported against its concentration gradient into the vesicles as there’s a transporter that removes 2 h+ ions from the cell in replace of a glutamate molecule entering the vesicle
  • The acidic env of the cell is achieved by a proton pump which uses the conversion of ATP to ADP to move h+ ions against their conc gradients
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11
Q

Describe the release of glutamate

A

Calcium dependent vesicular release at the axon end terminal bouton
-A depolarisation along the pre-synpatic neurone opens voltage dependant calcium channels. Calcium flows into the cell across its huge conc gradient

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12
Q

Outline the different receptors involved in glutamate transmission

A
  1. ) Ionotropic receptors iGluR (ion channels activated by glutamate)
    - NMDA cation channel na+ k+ ca2+
    - AMPA cation channel Na+ K+ (Some ca2+)
    - Kainate cation channel Na K+
  2. ) Metabotropic receptors mGluR ( G-protein coupled receptors, class C)
    - Interfere with the metabolism of the cell
    - Group I- mGluR1 & mGluR5 couple to Gq & G11 G proteins
    - Group II- mGluR2 & mGluR3 couple to Go& Gi G-proteins
    - Group III- mGluR4 & mGluR6-8 couple to Go& Gi G proteins
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13
Q

What are the differences in characteristics between G protein coupled receptors and ionotropic recepotrs?

A

G protein coupled receptors are slower because the receptor has to bind to glutamate and interact with a 2nd messenger system before having an effect

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14
Q

Outline the structure of the iGLUR receptor

A
  • 3 transmembrane units
  • 4 subunits; heterotetramer
  • Binding site for glutamate on N terminals
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15
Q

Outline the structure of the mGluR receptor

A

7 transmembrane proteins

-Binding site for glutamate on N terminals

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16
Q

Outline the reuptake of glutamate

A
  • In the astrocyte glutamate is converted to glutamine using glutamine synthase
  • Glutamine transporters present on the astrocyte and neurone allow the glutamine to be transported into the neurone
  • Glutaminase is used to convert glutamine back to glutamate
  • Excitatory amino acid transporters present on the neurone and glial cell also allow glutamate to be taken up
17
Q

Outline the degradation of glutamate

A
  • Excitatory amino acid transporters present on the neurone and glial cell allow glutamate to be taken up. This allows for removal from the synaptic cleft
  • Converted to glutamine by glutamine synthase in astrocytes
  • The glutamine is transferred to the neurone where it is converted back to glutamate by glutaminase to be reused
18
Q

Describe which drugs affect the transmission of glutamate

A
  1. ) Ketamine( NMDA channel blocker)
  2. ) Memantine ( NMDA competitive antagonist)
    - Used in AD to reduce neurodegenration of nerve cells in the brain
  3. ) Perampanel( noncompetitibe AMPA anatagonist)
    - useful anti-epileptic agent
19
Q

Describe the disease associated with Glutamate

A

Recreational drugs:
-phencyclidine (PCP) ‘angel dust@

disease: epilepsy-critical to all CNS function
- AD
- Drug abuse
- Anaesthesia

20
Q

Outline the characteristics of GABA(Gamma Aminobutyric acid )

A
  • AA
  • Widely distributed in the CNS (30% of synpases)
  • Very little in the PNS
  • The most important inhibitory NT in the CNS
21
Q

Describe the synthesis of GABA

A

-Glutamate is the precursor and it is converted to GABA using the enzyme GAD( Glutamic acid decarboxylase)

22
Q

Describe the storage of GABA

A
  • Similar idea to glutamate
  • vesicular GABA transporter (vGABAT) transports a GABA molecule into the vesicle in exchange for two protons
  • proton pump creates acidic environment using energy from conversion of ATP to ADP
23
Q

Describe the release of GABA

A

calcium dependent vesicular release axon end terminal bouton

24
Q

Outline the receptors involved in transmission of GABA

A
  1. ) Ionotropic receptors ( ion channels activated by GABA)
    - GABA(A) receptor: anion channel Cl-
  2. ) Metabotropic ( G-protein coupled receptors activated by GABA, class C)
    - GABA(B) receptors couple to Gi & Go G-proteins
25
Q

Describe the structure of receptors for GABA

A
  1. ) GABA(A):ionotropic receptor; 4 transmembrane regions; 5 subunits; when GABA binds it opens the cl- pore
  2. ) GABA(B): 7 transmembrane regions
26
Q

What effect do benzos have on GABA receptors?

A
  • Enhance the effect of GABA
  • -specific site for benzos to act on the GABAa receptor, they enhance its effect
  • Result in sedative, hypnotic, anxiolytic, anticonvulsant & muscle relaxant properties
  • eg diazepam & midazolam
27
Q

Describe the reuptake of GABA

A
  1. ) GAT1 = neuronal GABA transporter (requires na+)

2. ) GAT3= Glial GABA transporter

28
Q

Outline the degradation of GABA

A
  • Mostly occurs in glia
  • Using the enzyme GABA transaminase GABA is converter to succinic semialdehyde
  • Using the enzyme GABA transaminase, alpha-oxoglutarate is converted to glutamate
29
Q

Outline the Drugs that may act on different stages of GABA transmission

A
  1. ) acting on the receptors:
    - GABA(A) muscimol( agonist); bicuculline (competitive antagonist); picrotoxin (channel blocker); benzos; ethanol and some general anaesthetics(propofol are all positive allosteric modulators (PAMs)
    - GABA(B) baclofen(agonist); saclofen (competitive antagonist)
    - Reuptake tiagabine (blocks GAT)
    - degradation vigabatrine ( blocks GABA-transaminase)
30
Q

Outline the recreation drugs associated with GABA

A
  • Barbiturates “Downers”

- Nitrous oxide “laughing gas”

31
Q

Outline the diseases that may be associated with problems with GABA

A
  • epilepsy
  • anxiety
  • insomnia
  • muscle tone

Ageing block (16 decks)

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