Inhibitory Neurons

Question 1

How is glutamate converted to GABA?

Answer 1

Glutamic acid decarboxylase (GAD)

Question 2

How is GABA packed in vesicles?

Answer 2

By a vesicular inhibitory amino acid transporter (VIAAT). Sometime it is called VGAT.

Question 3

What role does vitamin B6 play in GABA synthesis?

Answer 3

It makes a GAD co-factor called pyridoxal phosphate. If people don’t have enough B6, they won’t be able to make GABA and might have seizures due to the lack of inhibitory NTs

Question 4

What happens to GABA in the synaptic cleft?

Answer 4

It is removed by GABA transporters (GAT) in both membrane of the glial cells and of the and of the axon terminal

GAT 1 is on neurons
GAT 3 is on glial cells

Both mop-up excess.

Question 5

Which GABA receptor is metabotropic?

Answer 5

GABAb

Question 6

Which GABA receptors are ionotropic?

Answer 6

GABAa and GABAc

Question 7

Where is glycine most important?

Answer 7

In the spinal chord inhibitory synapses

Question 8

What are glycine’s precursors?

Answer 8

Glucose becomes serine, which is converted to glycerin by serine hydroxymethyl transferase.

Question 9

What is glycine vesicular packaging protein?

Answer 9

The same as GABA. Vesicular Inhibitory Amino Acid Transporter (VIAAT). Interestingly there is some evidence that GABA and glycine can be packaged into the same vesicles.

Question 10

How is glycine removed from the synaptic cleft?

Answer 10

Via transporters on the neuron and glial cells

Question 11

Describe the structure of GABA and glycine receptors?

Answer 11

They are pentameric, they have five subunits, each with four domains. Structurally similar to ACh receptors.

The structure of glycine receptors is similar, glycine can require up to three molecules to open. Thus they have there alpha subunits.

Question 12

What sort of residues are on the M2 domain of GABA and glycine receptors?

Answer 12

neutral or positive so they can section for anions and bring chloride into the cell.

Question 13

What is chlorine’s reversal potential?

Answer 13

-70

Question 14

If the reversal potential is above AP threshold what type o synapse is it?

Answer 14

Excitatory

Question 15

If the reversal potential is below AP threshold what type of neuron it?

Answer 15

Inhibitory

Question 16

What has a large singles channel conductance GABA or glycine?

Answer 16

Glycine

Question 17

What type fo transporter exists in immature neuron that is taken out during development?

Answer 17

In a immature neuron there is a transporter that takes Na, K and Cl into the neuron. When the neuron is loaded up with chloride, the reversal potential shifts far to the right making GABA an excitatory neuron.

In mature neurons this is replaced with channels that take K and Cl out of the cell.

Question 18

How benzo work?

Answer 18

GABAa agonist. Send more chloride into the cell. The neurons being inhabited are in the spinal cord

Question 19

What is picrotoxin?

Answer 19

A plant derivative that blocks GABAa receptors channels and can be used to treater barbiturate overdoes

Normally a bad thing, can cause seizes

Question 20

How do barbiturates work?

Answer 20

They embed themselves in the channel and increase chloride pass through. GABAa

Question 21

How does propofol work?

Answer 21

Makes the chloride channels stay open longer. GABAa

Question 22

What happens glycine receptors don’t open?

Answer 22

Not enough inhibitory transmission in the spinal cord and the people over respond and can’t stop responding once a response has started

Question 23

What poison used glycine receptors?

Answer 23

strychnine. seizures and muscle spasms, eventually death asphyxiation. It is a glycine antagonist

Question 24

How do metabotropic GABA receptors work?

Answer 24

GABA binds to GABAb, it actives a Gi-protein, which inhibits cAMP production. cAMP would have acted to reduce the activity of K channel. Ultimately active GABAb enhances voltage gated K channel activity and inhibiting voltage gated Ca channel activity.

Moreover, calcium can flow out of the cell and prevent it from depolarizing and preventing Ca from flowing into the cell prevents it from depolarizing.

Very important for controlling spasticity

Question 25

Describe te structure of GABAb

Answer 25

It has seven transmembrane pass receptors and it activates a Gi-protein

Question 26

Discuss the pharmacological use of GABAb agonist baclofen

Answer 26

Controls involuntary muscle spasms in people that have certain forms of spasticity. Some people people will have a pump implanted, so that it releases at a sufficient level to quiet spinal nerves