neurotransmitters Flashcards
what is glutamate
an amino acid that can be synthesised in all cells - metabolic glutamate and transmissible glutamate
how is glutamate synthesised
from glucose via TCA and GABA-T in krebs cycle
from glutamine by glutaminase
how is glutamate processed and released from cells
- glutamate made in neuron
- loaded into synaptic vesicle via V-GLUT
- on Ca2+ influx, synaptic vesicle releases glutamate into synapse
- glutamate is taken up into astrocyte or neuron via EAAT
what are the two types of glutamate receptors
metabotropic glutamate receptors - mGluRs - GPCR
ionotropic glutamate receptors - ligand gated ion channels
what are mGluRs
GPCRs belonging to C class with large extracellular N-terminal where glutamate binds
8 subtypes mGluR1-8 split into three groups
what are the three mGluR groups
group 1 - mGluR1 and 5
- post synaptic and excitatory
- G alpha Q/11 - increases calcium
group 2/3 - mGluR 2/3 (2) mGluR 4-7 (3)
- presynaptic neuromodulation inhibitors
- G alpha i/o - decreases cAMP
what are the three classes of ionotropic glutamate receptors
NMDA
AMPA
Kainite
- all respond to different synthetic glutamate analogues
- all have similar structures - tetramers
what are NMDAR
- receptors that only respond to Lglutamate and NMDA
- tetrameric that forms a hetero-tetramer of 7 potential subunits
- usually 2GluN1 and 2GluN2
- receptor composition affects properties of receptor
- selective for Na, Ca, K
what are the 5 binding sites present on NMDAR
- glutamate - agonist site
- glycine
- polyamine
- Mg2+
- channel blocking site
how does glutamate bind to NMDAR
each tetramer binds to two molecules of glutamate, requires co-agonist of 2 glycine (D-serine or D-alanine) at GluN1
what competitive agonists can act at the glutamate site on NMDAR
D-AP5
what antagonists can bind to the glycine site on NMDAR
kynurenic acid and CGP 61594
what is the polyamine site on NMDAR
modulator site at amino terminal domain - allosteric modulators - can increase responses
what is the Mg2+ side on NMDAR
Channel is blocked by Mg 2+ at resting neuronal membrane potentials giving NMDAR voltage dependant channel block
what is the channel blocking site on NMDAR
allows for binding when the channel is open - ketamine, memantine
what are AMPAR
ligand gated ion channels that only respond to AMPA and L glutamine - forms a homotetramer or mixed heterotetrametric - impermeable to calcium and mediates fast excitatory transmission
what are KAINITER
ligand gated ion channels that only respond to kainite and L glutamine - structurally similar to AMPAR
what is end plate potential (EPP)
EPP is very large and activates an action potential in the muscle cell which then propagates - type of EPSP
what is EPSP
excitatory post synaptic potential
where are EPSPs formed in the CNS
pre-synaptic neurons - input from many presynaptic neurons is required to generate an action potential - Depolarisation eventually reaches threshold for firing
what are glutamergic receptors
excitatory receptors with round synaptic vesicles and large postsynaptic density
what are GABA receptors
inhibitory receptors with flattened synaptic vesicles with less postsynaptic density
what is post synaptic density
Receptors are clustered by lots of regulatory proteins into areas called a postsynaptic density - usually containing AMPAR (fast) and NMDAR (slow)
which protein is responsible for clustering receptors
PSD-95 - contains PDZ for protein-protein binding - binds directly to NMDAR but binds to TARP to regulate AMPAR
