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
What do NMDA and AMPA vary in terms of?
Their kinetics
AMPA only - when glutamate is released, sharp peak but then downward decay, receptor opens and closes really fast
NMDA - slow, positive current coming in so gradual peak, transmission lasts longer, slow kinetics
What is AMPA and kainate permeable too?
Na and K
fast opening channels
What is NMDA permeable too and how?
Slow opening channels, to calcium as well as NA and K
but..
requires glycine as a cofactor
and gated by membrane voltage - lots of depolarisation
they are only activated in an already depolarised membrane in the presence of gluatamate
What does stimulation of the presynaptic neuron lead too?
The release of glutamate, which binds to both receptor, but weak stimulation = AMPA receptors activated, strong stimulation = NMDA
What does calcium do in the NMDA receptor?
Acts as a second messenger, activates other intracellular cascades
What happens when NMDA receptors are out of sync?
Schizophrenia - when blocked by PCP, produces symptoms that resemble hallucinations associated with schizophrenia
certain antipsychotic drugs enhnance the flow of NMDA channels
Glutamate excitotoxicity -caused by excessive calcium influx into the cell, activating calcium dependent things which damage the cell, this occurs after a stroke and with some epilepsies and diseases - too much activation = neuron death
What does glutamate play a role in?
How we learn
