L20 - glutamate receptors

Question 1

what is the major excitatory NT in the brain

Answer 1

glutamate

Question 2

what does the activation of glutamate do

Answer 2

causes depolarisation

Question 3

how is glutamate syntheisised

Answer 3

from glucose (Krebs cycle) or glutamine (glial cells)

Question 4

what is the role of astrocytes in glutamate synthesis

Answer 4

Astrocytes recycle glutamate and
convert it back to glutamine which is
“inactive” ready to resupply neurons

Question 5

what are the two types of glutamate receptors

Answer 5

1) Ionotropic (ligand ion channels)
2) Metabotropic (G protein coupled receptors)

Question 6

what are examples of ionotropic receptors

Answer 6

NMDA receptor (N-methyl-D-aspartate)

AMPA receptor (a-amino-3-hydroxy-5-
methyl-4-isoxazolepropionic acid)

Kainate receptor - similar to AMPA

Question 7

structure of ionotropic receptors

Answer 7

Composed of 4 subunits

Question 8

how does binding occur at ionotropic receptors

Answer 8

Glutamate (i.e. the ligand) binds to the ligand-binding domain, causing a
conformational shift and change in the angle of the transmembrane domain,
opening the pore and an influx of cations

Question 9

AMPA receptor subunits

Answer 9

AMPA receptors that lack GluA2

Question 10

AMPA transmission

Answer 10

high permeability to calcium, mediate fast contraction

Question 11

location of AMPA receptor

Answer 11

Located throughout dendrites during
development and become concentrated at the postsynapse

Question 12

NMDA receptor subunits

Answer 12

composed of GluN subunits

Question 13

location of NMDA receptors

Answer 13

Usually co-located with AMPA receptors

Question 14

NMDA transmission

Answer 14

Mediates the slower component of excitatory neurotransmission in association with the rapid function of AMPA, highly permeable to calcium

Question 15

NMDA activation of neurotransmission

Answer 15

Are LGIC gated and activated by binding of glutamate and glycine (extracellular)

Voltage gated by a magnesium block that is triggered by membrane depolarisation induced by AMPA

Question 16

what are Silent synapses

Answer 16

excitatory synapses with NMDA but no
AMPA receptors

Question 17

metabotropic glutamate receptors

Answer 17

subtypes mGluR 1-8 divided into 3 groups
G protein coupled receptors that bind glutamate leading to an influx of calcium through indirect ion channel opening/secondary signalling

Question 18

group 1 mGluRs

Answer 18

mGluR 1, 5 binding Gq

Question 19

group 2 mGluR

Answer 19

mGlu 2, 3 binding Gi/o

Question 20

Group 3 mGlurs

Answer 20

mGlu 4, 6, 7, 8 binding Gi/o

Question 21

what is synaptic plasticity

Answer 21

the strengthening (long term potentiation) and weakening (long term depression) of the synapse in response to learning

Question 22

if a synapse gets stronger what does that mean for the postsynaptic neuron

Answer 22

the synapse is adjusting the response of the PSN to be greater

Question 23

how does AMPA strengthen a synapse

Answer 23

ampa receptors are trafficked to the PSN to increase the excitability of the response the opposite is true for synaptic weakening

Question 24

how is synaptic plasticity mediated

Answer 24

mGluRs and NMDA receptors recruit the calcium pathways that increase the
amount of AMPA receptors that are sent to the synapse

Question 25

MOA of ketamine

Answer 25

Blocks NMDA receptors, but no highly selective Has a slow “off rate” – after glutamate dissociates from the NMDAr, ketamine remains trapped inside the receptor leading to a prolonged block

Question 26

uses of ketamine

Answer 26

- Hypnotic and psychomimetic effects - Analgesia - Increases sympathetic activity - Maintains airway tone and respiration

Question 27

Perampanel moa

Answer 27

Antagonist for AMPA receptors (negative allosteric modulator) - Does not inhibit NMDA or kainate receptors Prevents the overstimulation of AMPA receptors

Question 28

uses of perampanel

Answer 28

treats epilepsy