Glutamate

What is glutamate synthesised from?

Glutamine

What is the major transport mechanism for extracellular glutamate removal in the central nervous system

excitatory amino acid transporters (EAAT)

What other than EAAT may play a role in glutamate uptake and removal?

aspartate and N-acetylaspartyl glutamate (NAAG)

How is glutamate formed?

glutamine transported from glial cells by glutamine transporters and then phosphate activated glutaminase forms glutamate from it

What happens to glutamate that is travelled back up by EAAT into presynaptic terminal or by EAAT to glial cells ?

transformed back to glutamine by glutamine synthase

What are the three classes of ionotropic receptors for glutamate?

NMDA, AMPA, KAINATE

What mGlu are in group I?

mGlu1, mGlu5

What are non-competitive NMDA receptor antagonists

Ifenprodil, Zn2+

What mGlu are in group II?

mGlu2, mGlu3

List 5 channel blockers for NMDA receptors?

Ketamine, PCP, Mg2+, MK801, memantine

What mGlu are in group III?

mGlu4, mGlu6, mGlu7, mGlu8

If the ampa receptor doesn’t have GluA2 subunit what does this mean for it?

also permeable to Ca2+

What are the agonists of AMPA receptor?

glutamate, AMPA, KA

What are the antagonists of AMPA receptor?

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

How fast is AMPA receptor transmission?

fast excitatory since over in 5 ms

What is the NMDA receptor permeable to?

sodium and calcium ions in, potassium out

What are unusual features of NMDA receptor?

voltage and ligand gates, need glycine/serine as co-agonist

In NMDA and AMPA will an action potential fire if close enough in potential?

yes, since excitatory

What happens when membrane potential is more positive -40mV in NMDA receptor?

relieves magnesium block

How does glycine/D-serine modulatory sites work?

glycine potentiates NMDA receptor mediated responses

What are competitive NMDA receptor antagonists?

AP5 and CPP

What are NMDA receptor ion channel blockers(and their affinity)?

ketamine (high affinity) and memantine (low affinity)

Where are group one mGlus generally found?

postsynaptic and produce slow depolarisation, release calcium from intracellular stores

Where are group two and three mGluRs generally found?

presynaptic, usually inhibit glutamate and other transmitters release

What glutamate receptors are found postsynaptically?

mGluR, KAR, AMPA, NMDA

What glutamate receptors are found presynaptically?

KAR, NMDA, mGluR

What kind of feedback does presynaptic NMDA do to control release?

positive feedback, so increase in it with increase glutamate release by increasing calcium reflux

What kind of feedback does presynaptic mGluR do to control release?

negative feedback, since increase in it reduces glutamate release since decreases calcium influx