NEURO: Neurotransmitter Systems I: Glutamate Flashcards
What are neurotransmitters?
What are the major central neurotransmitters?
chemical messengers that transmit signals from a neurone to a target cell across a synapse (e.g. neurotransmission)
Acetylcholine Glutamate GABA Glycine Monoamines
What is neurotransmission?
the process that drives information between neurones and their targets
What are the criteria of a neurotransmitter?
- The molecule must be synthesised and stored in the presynaptic neurone.
- The molecule must be released by the presynaptic axon terminal upon stimulation.
- The molecules must produce a response in the postsynaptic cell.
What is the major excitatory neurotransmitter?
glutamate
Nearly all excitatory neurons in the CNS are glutamatergic
Describe the synthesis of glutamate.
This type of neurotransmitter is known as an amino acid transmitter because its precursors are all amino acids.
Glutamine is converted to glutamate in nerve terminals, which is catalysed by glutaminase, which is phosphate-activated. It is synthesised in the nerve terminals.
Describe the transport of glutamate.
Glutamate is transported into vesicles by vesicular glutamate transporters (VGLUT).
There is an H+-Glu transporter on the vesicle membrane. We harness the passive process of H+ moving down its concentration gradient to get more glutamate into the vesicle.
Thus, the intracellular environment of the vesicles is really acidic.
Describe glutamine reuptake and degradation
Glutamate Receptors
Ionotropic Receptors:
· AMPA Receptors
· NMDA Receptors
· Kainate Receptors
Metabotropic Receptors:
· Group I
· Group II
· Group III
What is the response when glutamate activates the different ionotropic receptors?
With AMPA, we get the influx of Na+ and the efflux of K+.
With NMDA, we get the influx of Na+ and Ca2+, and the efflux of K+.
With Kainate, we get the influx of Na+ and the efflux of K+.
Describe AMPA receptors.
What do GluA2 subunits do?
There are 4 subunit types (plus alternative splice variants):
- GluA1
- GluA2
- GluA3
- GluA4
hetero-tetrameric - there are normally 2 pairs of two types of subunits. The most common orientation is GluA2 and GluA1/3/4.
The presence of GluA2 subunits prevents Ca2+ flow. Thus, they protect the brain against excitotoxicity.
How many binding sites does the AMPA receptor have? How many must be occupied for channel opening?
What are AMPA receptors most commonly comprised of?
Four orthosteric binding sites
Two sites must be occupied for channel opening
Current increases as more binding sites are occupied
- 2 GluA2 subunits
- 2 GluA1/3/4 subunits
Describe NMDA receptors.
What are NMDA receptors mostly comprised of?
There are three subunit types (plus alternate splice variants):
- GluN1 (or NR1)
- GluN2 (or NR2)
- GluN3 (or NR3)
It is also hetero-tetrameric.
The most common orientation is a pair of GluN1 subunits plus GluN2 (or 3). GluN3 subunits are inhibitory to NMDA receptor function.
What do GluN3 subunits do?
inhibit NMDA receptor function
Types of NMDA glutamate receptors
How many binding sites must be occupied for channel opening in NDMA receptors?
Ligand NMDA glutamate receptor
Ligand and Voltage-gated NMDA receptors
All the sites must be occupied for the channel to open.
> Glycine or D-serine binds GluN1
Glutamate binds GluN2
Voltage-gated NMDA glutamate receptor, how does it work?
> Glycine or D-serine binds GluN1
Glutamate binds GluN2
Mg2+ block at resting membrane potential
during depolarisation event, Mg2+ will move out and allow ions to move freely