Glutamate Flashcards
Where is glutamate synthesised?
In nerve terminals from glucose or glutamine
Where is it stored?
In vesicles by vesicular glutamate transporters
How is it released?
By exocytosis - influx of calcium (Ca2+) - it then binds and activates post synaptic receptors
How is the release stopped?
By reuptake excitatory amino acid transporters and glia which can vacuum it up
What happens if there is too much glutamate and not enough GABA?
Hyperexcitability - epilepsy, caused by stroke, infection of trauma
Excitotoxicity - cell death in the brain. Can get this from cerebral ischemia
What is cerebral ischemia?
Cell death in the brain due to insufficient blood flow due to plaque, tumour
symptoms: weakness, visual impairments
reversal of the Na and L gradient, transports release glutamate by reverse operation, the transporters don’t work
Excitotoxic death due to high glutamate - can cause permanent damage
What are the 3 glutamate receptors?
NMDA AMPA (dominant ones in excitatory) Kainate All agonists, binding to glutamate allows positive ions to come in
What do each receptors have?
An agonist and an antagonist
What is the AMPA receptor?
Ionotropic
Glutamate binding, leading to the opening of Na channels, so there is depolarisation
there is a selective agonist which responds to AMPA: AMPA
What is the NMDA receptor?
Glutamate can bind but needs a co-agonist (glycine) as well so it binds to NMDA - it is blocked at rest
What co-agonist does NMDA require and why?
Glycine because glutamate on its own means it is blocked - need 2 keys to open in
What is NMDA blocked by?
Magnesium Mg2+
Steps for the NMDA receptor
Ionotropic receptor
Permeable to Na, K, and Ca2+
binding of glutamate - nothing happens
at rest, glutamate binds, channel opens but is blocked by Mg2+
depolarised membrane, Mg2+ pushed out of pore, channel is open, ion movement, further depolarisation
How do you remove the NMDA block?
normal transmission - glutamate released, binds to AMPA, binds to NMDA but nothing happens
if excited, so lots of AMPA receptors open, the magnesium block is removed, glutamate binds, receptor opens, and sodium an calcium comes in
Difference between AMPA and NMDA in terms of what ions flow
AMPA - only sodium
NMDA - sodium and calcium
