GABA Flashcards

1
Q

Where is GABA synthesised from?

A

Glutamate - presynpatically

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2
Q

How is GABA stored?

A

By a vesicular GABA transporter

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3
Q

How is GABA released?

A

By calcium influx

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4
Q

Where does GABA act?

A

At ionotropic GABAa and metabotropic GABAb receptors

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5
Q

How is GABA cleared from synapse?

A

By reuptake using transporters on glia and neurons

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6
Q

What does too much GABA lead too?

A

Sedation/coma - because it produces inhibition

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7
Q

What can drugs which increase GABA transmission be used to treat - if at right dose?

A

Epilepsy - calm them down

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8
Q

Example of a GABA drug

A

GHB - date rape drug
a GABA metabolite than can be converted back to GABA by transamination, increases amount of GABA available, moderate dose like alcohol, but too much leads to unconscious and death

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9
Q

What does alcohol cause?

A

Unconsiousness, coma and death
the margin of safety is low, can get drunk from 0.2-0.3 but death is caused from 0.35-0.5 - luckily, people pass out before they reach this stage

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10
Q

What are the two GABA receptors?

A

GABAa - inotropic - lingad gated Cl- channels, fast IPSP’s

GABAb metabotropic receptors - G protein coupled receptors, indirectly coupled to K or Ca2+ channel through second messengers, opens k channel, closes Ca2+ channel. Slow IPSPS

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11
Q

What is the main difference between GABAa and GABAb?

A
GABAa = fast IPSPs
GABAb = slow IPSPs
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12
Q

What are GABAa receptors made of?

A

6 possible subunits

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13
Q

What happens when GABA is released to GABAa?

A

Cl channel gated by the binding of GABA
GABA increases chloride and hyperpolarises the neuron
Decreasing the depolarising effects of an excitatory neuron - counteracts excitation

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14
Q

Why is GABA complex?

A

Because it has multiple binding sites

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15
Q

What drugs bind at GABA binding site?

A

Muscimol (comes from mushroom: evolution purpose to protect themselves) - agonist - eat the fungi, get signs of drunk

Bicuculine - antagonist - get disinhibition, don’t have breaks, get excitation

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16
Q

What drugs bind elsewhere on the receptor? (no competition with gaba)

A
Benzodiazepine
Barbiturates
Ethanal
Neurosteroids 
all cause IPSPs
17
Q

What do drugs which increase GABA activity do?

A

Reduce anxiety - anxiolytic
for example:
agonists: alcohol and barbiturates
indirect agonist: benzodiazepines

18
Q

What do drugs which decrease GABA activity do?

A

Increase anxiety - antigenic
for example,
antagonist: flumazenil

19
Q

Is there evidence for GABA dysfunction in anxiety disorders?

A

Yes, patients with panic disorders have less benzodiazepine binding sites

They lack inhibitory control in corticol and limbic regions to suppress inappropriate fear responses and have a panic attack - because they have no GABAa receptors

The frontal cortex is hyperactive during periods of anxiety

20
Q

What are the actions of drugs at the GABAa receptor?

A

Barbiturate (agonist) - produces a full effect alone
Benzodiazepine (indirect agonist) - no effect alone, but in the presence of GABA has an effect
Flumazenil (antagonist) - no effect alone, if mixed with GABA, reduces the effect of GABAa receptor - blocking it

21
Q

What are the problems with barbiturates?

A

General depression of neuronal activity - causes functions to slow down
poor therapeutic ratio - small difference between dose and overdose - high suicide risk
long term treatment = withdrawal and dependence
only used for severe insomnia and seizures

22
Q

What is benzodiazepine?

A

Discovered in the 60’s, first one as librium. Then diazepam was the major treatment
acts as: anxiolytic, anticonvulsant, sedative, muscle relaxant, amnestic (memory)
good, fat acting, large therapeutic window
may cause dependence, if mixed with alcohol = depression