Glutamate

Question 1

What is glutamate?

Answer 1

The main excitatory transmitter in the CNS.

Question 2

What is glutamate synthesised from?

Answer 2

Glutamine.

Question 3

What reuptakes glutamate?

Answer 3

Excitatory Amino Acid Transporters (EAAT).

Question 4

What is the beginning of the process for glutamate synthesis?

Answer 4

Glutamine synthase creates glutamine which is transported out of the cell using a transporter.

Question 5

What happens when glutamine enters the neurone?

Answer 5

GLutaminase (phosphate activated) converts glutamine to glutamate which is stored in a vesicular transporter for synaptic transmission.

Question 6

What are the two types of glutamate receptors?

Answer 6

Ionotropic and metabotropic.

Question 7

How can glutamate bind so many receptors?

Answer 7

It is not a rigid molecule - they different parts of the molecule can rotate and adopt different conformations.

Question 8

How many rotamers of glutamate are possible?

Answer 8

9.

Question 9

What is the structure of the ionotropic glutamate receptors?

Answer 9

It is made up of 4 subunits (tetrameric) which each have 4 membrane segments. 1, 3 and 4 segments are trans-membrane and 2 does not span the membrane.

Question 10

What determines the properties of the ionotropic glutamate receptors?

Answer 10

The subunit composition.

Question 11

What is AMPA generally composed of?

Answer 11

4 of the same subunits - homomeric.

Question 12

What is NMDA composed of?

Answer 12

Different subunits - heteromeric. It cannot act as a receptor if it is homomeric.

Question 13

What is the AMPA receptor permeable to?

Answer 13

Na+ in and K+ out.

Question 14

What is the NMDA receptor permeable to?

Answer 14

Na+, K+ and Ca2+.

Question 15

What are the agonists of the NMDA receptor?

Answer 15

NDMA, glutamate and aspartate.

Question 16

WHat are the antagonists of the NMDA receptor?

Answer 16

2-AP5, CPP (competitive), PCP, ketamine, MK801 (non-competitive).

Question 17

What are the agonists of the AMPA receptor?

Answer 17

Glutamate, AMPA, KA.

Question 18

What are the antagonists of the AMPA receptor?

Answer 18

NBQX (competitive), GYKI 53655 (non-competitive).

Question 19

How is the NMDA receptor dually gated?

Answer 19

With glutamate alone, no current flows and Mg++ blocks the channel. If the membrane is depolarised, the Mg++ is removed and Ca and Na can flow through the channel.

Question 20

How can the NMDA receptor act as a transmitter and a voltage sensor?

Answer 20

As it needs glutamate and a voltage in order for Ca and Na to pass through.

Question 21

What is the Mg-dependent gating important in?

Answer 21

Synaptic plasticity, learning and memory.

Question 22

What are metabotropic receptors involved in?

Answer 22

Slow, neuromodulatory role.

Question 23

What are the three types of ionotropic glutamate receptors?

Answer 23

NMDA, AMPA and KA.

Question 24

What is the shortened name for metabotropic glutamate receptors?

Answer 24

mGluRs.

Question 25

What do mGluRs normally allow?

Answer 25

Ca++ in and K+ out.

Question 26

What happens when glutamate binds to mGluR?

Answer 26

Ca+ channel closes and there is a reduced influx. This controls the transmitter release. K+ channels close and there is a reduced K-efflux. This leads to slow depolarisation.

Question 27

What happens after glutamate is bound to mGluR?

Answer 27

Intracellular enzymes are activated and there is a second messenger cascade. Ca is released from intracellular stores and further enzymes are activated. There is opening and closing of ion channels and the modulation of postsynaptic excitability.

Question 28

What does presynaptic NMDAr do?

Answer 28

Increase glutamate release by increasing Ca influx.

Question 29

What does presynaptic mGluR do?

Answer 29

Decrease glutamate release by decreasing Ca influx.