21- Glutamate Flashcards
define a neurotransmitter
a chemical messenger that transmits signals from a neuron to a target cell across a synapse
what are the criteria for neurotransmitters? (3)
- molecule synthesised and stored in pre-s neurone
- molecule released by pre-s axon terminal when stimulated
- molecule produces a response in the post-s cell
how are neurone classified?
based on differential gene expression of proteins involved in NT synthesis, storage and release
differences in neuronal structure
define glutamate
the major excitatory NT in the CNS
nearly half of all CNS excitatory neurons are glutamatergic
describe the synthesis of glutamate
glutamine converted to glutamate by glutaminase, a phosphate activated enzyme
glutamate is synthesised in nerve terminals
describe glutamate transport into (pre)synaptic vesicles
glutamate transported into synaptic vesicles by VGLUT transporter = different VGLUT subtypes involved
transported via a counter-transport process = vesicle environment is acidic maintained by an ATP-driven proton pump which pumps H+ down a conc. grad into the vesicle
drives glutamate entry into vesicle via VGLUT transporter
describe glutamate reuptake from the synaptic cleft
EAATs transporters on glial cells and neurons - Na+ ion dependent co-transporters
transporters take glutamate from the synaptic cleft into pre-s neurons/ glial cells
describe glutamate degradation
glutamate converted to glutamine via glutamine synthase in glial cell
glutamine exported out of glial cells by SN1
glutamine transported into neurons by SAT2
creates a glutamine-glutamate cycle for synthesis and degradation
what does EAATs stand for?
excitatory amino acid transporters
what are the two types of glutamate receptors and their subtypes
ionotrophic/LGIC:
- AMPA receptors
- NMDA receptors
- kainate receptors
metabotrophic/GCPR:
- group 1 = mGlu 1,5
- group 2 = mGlu 2,3
- group 3 = mGlu 4, 6, 7, 8
describe the ionic movements through each of the ionotropic glutamate receptors
all allow Na+ influx and K+ efflux
NMDA receptors also allow Ca2+ influx = important for long term potentiation
describe the AMPA receptor
post-synaptic receptor, consists of four subunits = GluA1-4 with alternate splice variants
receptor composed of four subunits, hetero-tetrameric:
- two GluA2 subunits
- two of GluA1/3/4 in any combination
presence of GluA2 subunits makes the receptor impermeable to Ca2+ activity - Ca2+ has many excitatory intracellular effects, meaning GluA2 serves a protective role against potential excito-toxicity
receptor has 4 orthosteric binding sites, only two need to be occupied for IC opening
significance of GluA2 subunit?
makes the receptor impermeable to Ca2+ activity
protects against potential excito-toxicity
describe the NMDA receptor
three subunit types with alternate splice variants - GluN1-3
hetero-tetrameric receptor composed of four subunits
- two GluN1
- two GluN2 or two N3 = N3 is inhibitory to NMDA receptor function
has ligand-gated and voltage-gated properties
- ligand-gated = glutamate binds to N2, glycine/D-serine binds to N1. all four binding sites must be occupied for the IC to open
- voltage gated = Mg2+ ion blocks the C at resting membrane potential. with depolarisation, the Mg2+ moves, allowing ion passage through the IC
describe the kainate receptor
5 subunit types with alternate splice variants = GluK1-5
GluK1-3 can form homomers or heteromers
GluK4 and 5 can only form heteromers with GluK1-5
less is known about this receptor, don’t know number of glutamates that need to bind for IC to open. distributed less in the brain.