Glutamate and GluRs

Question 1

Glutamate is the most….

Answer 1

prominent neurotransmitter in the body, and is the main excitatory NT

Question 2

How many Glu receptors are there, and are they metabotropic or ionotropic?

Answer 2

6 types, 3 ionotropic, 3 metabotropic

Question 3

What are the three different ionotropic GluRs and how many of each is there?

Answer 3

AMPAR (4), NMDAR (7) and kainate R (5)

Question 4

What are the general topology of the ionotropic GluRs?

Answer 4

Tetrameric, each monomer consists of 3 TMs and one reentry loop. The ligand binding pocket (clamshell-like) consists of the N-terminal and the loop between M2 and M3. The pore is mainly made up of the M3s, but the M2 forms the selectivity filter. The symmetry changes through the TMD to the ATD from 4-fold to 2-fold

Question 5

Are all the ionotropic GluRs homomeric?

Answer 5

No, the NMDR consists of 2 NR1 subunits, and 2 NR2 subunits. The 2 NR1 subunits binds the coagonist (either gly or D-ser)

Question 6

Which ion can block the pore of NMDAR?

Answer 6

Mg^2+

Question 7

Which ions are permeable through the iGluRs?

Answer 7

Mainly Na^+ (AMPAR) and Ca^2+ (NMDAR)

Question 8

How is glu involved with learning and memory?

Answer 8

AMPAR binds glu resulting in Na^+ influx inducing depolarization, that displaces the Mg^2+ from the NMDAR. Then NMDAR can be gated, resulting in Ca^2+ influx and AP. Ca^2+ also induce LTP , by CaMK activation, induceing phosphorylation and trafficking of a preexisting AMPAR pool to the presynaptic membrane

Question 9

What are LTP?

Answer 9

Long-term potentiation: a persistant strengthening of synapses caused by a long-lasting increase in signal transmission

Question 10

What are the topology of the metabotropic GluRs, and which G-proteins are they coupled to?

Answer 10

Family C GPCRs: homodimers. Group 1 are Gq coupled, while group 2+3 are Gi coupled

Question 11

PCP is an antagonist of the NMDAR, and can induce….

Answer 11

schizophrenia-like symptoms