Glutamate Flashcards
What is glutamate?
The main excitatory transmitter in the CNS.
What is glutamate synthesised from?
Glutamine.
What reuptakes glutamate?
Excitatory Amino Acid Transporters (EAAT).
What is the beginning of the process for glutamate synthesis?
Glutamine synthase creates glutamine which is transported out of the cell using a transporter.
What happens when glutamine enters the neurone?
GLutaminase (phosphate activated) converts glutamine to glutamate which is stored in a vesicular transporter for synaptic transmission.
What are the two types of glutamate receptors?
Ionotropic and metabotropic.
How can glutamate bind so many receptors?
It is not a rigid molecule - they different parts of the molecule can rotate and adopt different conformations.
How many rotamers of glutamate are possible?
9.
What is the structure of the ionotropic glutamate receptors?
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.
What determines the properties of the ionotropic glutamate receptors?
The subunit composition.
What is AMPA generally composed of?
4 of the same subunits - homomeric.
What is NMDA composed of?
Different subunits - heteromeric. It cannot act as a receptor if it is homomeric.
What is the AMPA receptor permeable to?
Na+ in and K+ out.
What is the NMDA receptor permeable to?
Na+, K+ and Ca2+.
What are the agonists of the NMDA receptor?
NDMA, glutamate and aspartate.
WHat are the antagonists of the NMDA receptor?
2-AP5, CPP (competitive), PCP, ketamine, MK801 (non-competitive).
What are the agonists of the AMPA receptor?
Glutamate, AMPA, KA.
What are the antagonists of the AMPA receptor?
NBQX (competitive), GYKI 53655 (non-competitive).
How is the NMDA receptor dually gated?
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.
How can the NMDA receptor act as a transmitter and a voltage sensor?
As it needs glutamate and a voltage in order for Ca and Na to pass through.
What is the Mg-dependent gating important in?
Synaptic plasticity, learning and memory.
What are metabotropic receptors involved in?
Slow, neuromodulatory role.
What are the three types of ionotropic glutamate receptors?
NMDA, AMPA and KA.
What is the shortened name for metabotropic glutamate receptors?
mGluRs.
What do mGluRs normally allow?
Ca++ in and K+ out.
What happens when glutamate binds to mGluR?
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.
What happens after glutamate is bound to mGluR?
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.
What does presynaptic NMDAr do?
Increase glutamate release by increasing Ca influx.
What does presynaptic mGluR do?
Decrease glutamate release by decreasing Ca influx.
