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Ageing > Glutamate And GABA > Flashcards

Glutamate And GABA Flashcards

1
Q

Is Glutamate an excitatory or inhibitor NT?

A

Excitatory

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2
Q

Where is glutamate most widely distributed in the body?

A

70% in the CNS

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3
Q

How is glutamate made in the neurone?

A

Glutamine is converted to glutamate by Glutaminase. Then it is degraded to alpha-oxoglutarate by transaminase

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4
Q

How it glutamate formed in Glia cells?

A

Alpha-oxoglutarate is converted to glutamate by GABA transaminase. It is degraded to Glutamine by Glutamine synthase

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5
Q

What are the three different types of vesicular-glutamate transporter pumps?

A

VGluT1
VGluT2
VGluT3

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6
Q

What is transported out of the vesicle in order for glutamate to be transported into the vesicle?

A

2 x H+ ions

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7
Q

How is the inside of the storage vesicle kept at a low pH?

A

Another proton pump/ATPase which pumps H+ into the cell against it’s concentration gradient. Needs ATP

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8
Q

Which channels opens after depolarisation occurs to release the glutamate form the vesicle?

A

Voltage gated Ca channels

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9
Q

What are the three ionotropic glutamate receptors? (Ion channels activated by glutamate)

A

NMDA cation channel - Na, K, Ca
AMPA cation channel - Na, K, (some Ca)
Kainate cation channel - N, K

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10
Q

What are the three metabotropic receptors what glutamate acts upon? (G-protein coupled receptors, Class C)

A

Group 1 - mGluR1 + mGluR5 couple to Gq and G11 G-proteins
Group 2 - mGluR2 + mGluR3 couple to Go and Gi G-proteins
Groups 3 - mGluR4 + mGluR6-8 couple to Go and Gi G-proteins

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11
Q

What is the structure of Inotropic glutamate receptor?

A

Heterotetromer
Bind to glutamate at the N terminus
3 alpha helices and inverted P loop

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12
Q

What is the structure of the G-coupled glutamate receptors?

A

7 transmembrane domains
Binding site outside on the N terminus
Coupling region on the third intracellular loop
Activate second messenger system

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13
Q

How is glutamate recycled?

A

Either taken up into the glial cells where it is converted to glutamine or repackaged into vesicles in the neurone

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14
Q

How is glutamate removed from the synaptic cleft?

A

EAAT

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15
Q

Which drugs work on the NMDA glutamate receptor?

A

Ketamine - channel blocker

Meantime - competitive antagonist

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16
Q

Which drug works on the AMPA glutamate receptor?

A

Perampanel - noncompetitive antagonist

17
Q

Which recreational drugs involved the glutamate receptors?

A

Ketamine

PCP (phencyclidine)

18
Q

Which diseases can be therapeutically controlled by manipulation of the glutamate receptors?

A

Epilepsy
Alzheimer’s
Anaesthetic

19
Q

Is GABA an inhibitory or excitatory neurotransmitter?

A

Inhibitory

20
Q

How is GABA made?

A

From glutamate via the glutamic acid decarboxylase enzyme (GAD)

21
Q

What is the name of the transporter which concentrates GABA into it’s storage vesicle?

A

Vesicular GABA transporter

22
Q

What is needed for release of GABA from the vesicles?

A

Ca influx

23
Q

Which ionotropic receptors are activated by GABA?

A

GABAa receptor - anion Cl-

24
Q

Which metabotropic receptors do GABA work on?

A

GABAb receptors coupled to Gi and Go proteins

25
Q

What is the structure of the ionotropic receptor GABAa?

A

Heteropentomer - 5 subunits
2 binding sites for GABA
Cl- pore in the middle so when GABA binds, Cl- ions can flow through in the cell

26
Q

What is the structure of the metabotropic GABAb receptor?

A

7 transmembrane units
GABA binds to N terminus
Third loop modifies cell’s biochemistry

27
Q

How is GABA removed from the synaptic cleft?

A

Via the reuptake protein

28
Q

Which reuptake proteins are present on neurones?

A

GAT1

29
Q

Which reuptake proteins are on astrocytes, in particular glial cells?

A

GAT3

30
Q

How is GABA degraded?

A

It is broken down to Succinic semialdehyde via the GABA transaminase

31
Q

Which drugs act via the GABAa receptor?

A

Benzodiazepines, alcohol and some general anaesthetics (propofol) are all positive allosteric modulators

32
Q

Which drugs work via the GABAb receptors?

A

Baclofen (agonist)

Saclofen (competitive antagonist)

33
Q

Which two drugs used in Epilepsy work via the GABA system and how?

A

Tiagabine - blocks GAT

Vigabatrine - blocks GABA-t

34
Q

Which recreational drugs work via the GABA system?

A

Barbiturates

Nitrous oxide

Ageing (3 decks)

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