GABAergic neurotransmission

Question 1

main purpose of GABA

Answer 1

major inhibitory neurotransmitter of cns.

Question 2

synthesis of GABA

Answer 2

glutamate ——1——-> GABA

Done by GAD - glutamate acid decarboxylase

Question 3

GAD

Answer 3

• cystolic (found in GABAergic neurons however recently found in non neural tissue.
• two isoforms, that differ slightly in molecular weight:

—GAD65 and GAD67

-inhibition of GAD causes –> CONVULSION

Question 4

Degradation of GABA steps

Answer 4

GABA + a-ketoglutarate —> succinic semialdehyde + glutamate

enzyme: GABA Transaminase (GABA-T)

Question 5

location and inhibition of GABA-T

Answer 5

location: -Mitochondrial

inhibited by: gamma-vinyl-GABA (tradename - Vigabatrin)

-it irreverisbly binds to GABA-T which leads to higher amount of synaptic GABA

THUS—> NOVEL ANTIEPILEPTIC EFFECT

Question 6

what is used in the GABA shunt

Answer 6

when GABA is catabolised into -> Succinic Semialdhyde

it can enter the TCA cycle with the action of:

->Succinic Semialdehyde dehydrogenase.
(uses NAD+ and H2O)

Question 7

What uptakes Glutamate in presynaptic neuron?

Answer 7

vglut

Question 8

How can glutamate enter the citric cycle?

Answer 8

glutamate dehydrogenase

Question 9

Name of protein which uptakes glutamate on glutametergic neuron?

Answer 9

EAAT2 (also found on astrocytes)

Question 10

Name of the glutamate uptaker on astrocytes?

Answer 10

EAAT1 (onlz found on astrocytes)

Question 11

name of protein which takes up GABA into vesicles?

Answer 11

vGAT

Question 12

name of transporter for GABA?

Answer 12

GAT

Question 13

properties of GAT

Answer 13

found in

• neurons
• astrocytes (20% of GABa released is taken up by these)
• GAT is Na+ dependent.
• bidirectional
• it functions against concentration gradient

Question 14

fate of GABA when taken up by different cells

Answer 14

Glia - used for metabolism.

GABA —–gaba-t—> Glu (glu then converted to gln by gln synthase)

Neuron - reutilized in neurotransmission

Question 15

types of GAT and where they are expressed?

Answer 15

GAT1: - on presynaptic GABA neuron
GAT2: - extrasnaptic regions
GAT3: astrocytic processes

Question 16

inhibitors of GAT?

Answer 16

-anticonvulsants

Question 17

how many types of GABA receptors are there

Answer 17

two.

• GABA A receptor
• GABA B receptor

Question 18

what is the GABA A receptor

Answer 18

is a ligand gated chloride ion channel.

-causes hyperpolariation and thus decreases chance of AP forming.

Question 19

effects of GABA A receptor in different areas?

Answer 19

synapse: -rapid phasic inhibitory currents

extrasynaptic area: - tonic inhibitory currents

Question 20

what are GABA B Receptor

Answer 20

• dimeric G coupled receptor.

- structurally similiar to –> metabotrophic glutamate receptors

Question 21

effects of GABA B receptors

Answer 21

-linked to variety of effectors.

Some:

• open k+ channels thus cause inhibitory currents
• decrease Ca++ conductance
• inhibit cAMP production

Question 22

where do GABA B receptors act?

Answer 22

they mediate inhibition on:

-pre and post synaptic neurons.

Question 23

structure of GABA A Receptor

Answer 23

-pseudosymmetrical 5 subunit chloride channel

• each subunit has 4 transmembrane domains.
• subunits are composed of 19 different polypeptides.
• one of each subunit contributes to formation of the channel.
• each subunit has a phosphorylation site.

Question 24

GABA A receptor agonists

Answer 24

-benyodiazepines.

have :

-anticonvulsant and anxiolytic, sedative hypnotic effects.

Question 25

effect of ethanol on receptor

Answer 25

• affects GABA A receptor.

- enhances GABA action on the receptor.

Question 26

effect of barbituates on GABA A receptor

Answer 26

allosterically increase benzodiazepine and GABA binding to receptor.