Glutamatergic excitatory neurotransmission (week 8)

Question 1

what are the three main subtypes of ionotropic glutamate receptors

Answer 1

AMPA (a amino -3- hydroxy-5-methyl-4-isoxzolepropionic acid)
NMDA (N-methyl-D-aspartate receptors)
Kainate

Question 2

what is the structure of AMPA and ion selectivity

Answer 2

tetrameric complexes composed of combinations of GluA1, GluA2, GluA3, and GluA4 subunits.
primarily conduct sodium and potassium ions resulting in depolarisation of the post-synaptic neuron

Question 3

NDMA structure and ion selectivity

Answer 3

tetrameric complexes consisting of GluN1, GluN2 (A,B,C,D) and GluN3 (A,B) subunits
conduct Ca2+ and Na+ and K+ ions.
require both glutamate binding and post-synaptic membrane depolarisation for activation

Question 4

Kainate structure and ion selectivity

Answer 4

tetrameric, composed of GluK1, GLUK2, GLUK3, GLUK4, GLUK5 subunits.
mainly conduct Na+ and K+

Question 5

what blocks NMBA receptor

Answer 5

Mg2+

Question 6

what does NMDAR need to open

Answer 6

both glutamate and co-agonist glycine

Question 7

at -60mV what is the net flow

Answer 7

inwards varried by Na+ and Ca2+ entering cell.
Mg2+ jumps in to stop it.

Question 8

at +20mV what is net flow

Answer 8

outwards mainly carried by K+ leaving cell,
Mg2+ does not block the channel however at +40mV Mg2+ has no effect

Question 9

where is the glutamate binding site

Answer 9

GluN2 subunit

Question 10

where is the glycine binding site

Answer 10

GluN1 subunit

Question 11

what is the NMDAR antagonsist

Answer 11

APV

Question 12

what is the kinate and AMPA antagonist

Answer 12

CNQX

Question 13

what does the GLUA2 subunit impair

Answer 13

Ca2+ permeability and prevents polyamine block

Question 14

what is spermine and what does it act as

Answer 14

it is a polyamine and it acts as an intracellular AMPAR ion channel antagonist to block the outward current carried by cations.

It only blocks the GLUA2 subunit lacking AMPARs and the non-edited GLUA2 AMPARs

Question 15

what are most NMDARs composed of

Answer 15

GLUN1 + GLUN2 subunits

Question 16

what are quantun dots

Answer 16

Tiny semiconductor particles

Question 17

what must post synaptic receptor do for efficient synaptic transmission

Answer 17

cluster opposite presynaptic release sites

Question 18

summary of AMPA receptor trafficking in and out of the post synaptic density

Answer 18

1) Newly synthesized receptors are transported intracellularly in vesicles by molecular motors on microtubules.
2) Vesicle exocytosis in the dendritic shaft.
3) Once at the cell surface, receptors move randomly.
4) The receptors are reversibly stabilized by diffusion trapping at the post-synaptic density (PSD)through interactions with scaffold proteins.
5) Diffusing receptors internalized at extra synaptic endocytic zones by clathrin-dependent endocytosis.
6) Endocytosed receptors can be recycled back by exocytosis

Question 19

AMPA receptors are highly plastic meaning…

Answer 19

they change their location in response to a variety of physiological and pharmacological stimuli

Question 20

The expression & location of AMPARs is highly dynamic being influenced by

Answer 20

1) neuronal activity – a basis for synaptic plasticity e.g. LTP.
2) exposure to acute & chronic stress.
3) neurodegenerative disorders e.g. Alzheimer’s Disease, Huntington’s disease.
4) by various drugs – e.g. ketamine, cocaine.

Question 21

calcium influx through the NMDA receptors is necessary for what

Answer 21

signalling pathways that lead to the persistent strengthening of the synapse