EAA and Excitotoxicity Flashcards
What three things are vital to normal brain function
calcium, oxygen, EAA
What are the EAAs
Glu, Asp
Where does Asp typically work
Serves as neurotransmitter in visual cortex and pyramidal cells
What receptors are receptive to EAA
NMDA and non-NMDA
Function of NMDA
Influx of calcium
What is one of the binding sites in NMDA
Glycine binding site, specifically, with another EAA
What type of receptor is NMDA
Ionotropic
Where is the Mg binding site in NMDA
within channel itself, and blocks the channel
Function of Mg in channel
prevents calcium influx when channel is open, makes NMDA receptor both ligand and voltage gated
Where is the PCP binding site
In channel, beneath Mg
Function of PCP
Horse tranquilizer, blocks channel
non-NDMA function
primarily a Na influx
what type of receptor is non-NMDA
ionotropic
What are the types of non-NMDA receptors
AMPA and Kainate
What can bind to AMPA
EAA and Benzodiazepines
Function of AMPA
Na influx, when benzodiazepines bind it reduces the amount of Na that enters
What type of potential is formed by non-NMDA
typical excitatory post synaptic potential, relatively short onset and duration
What type of potential is formed by NMDA
long latency epsp with a long duration
Function of non-NMDA and NMDA together
non-NDMA opens first, Na flows in and depolarizes. typical epsp forms, causes enough depolarization to cause the Mg to leave NMDA channel, Ca then comes in and forms lasting epsp.
Functions of non-NMDA
primary sensory afferents, upper motorneurons
Function of NMDA receptors
critical in short and long term memory formation, synaptic plasticity
What types of EAA metabotropic receptors exist
G1: Gq coupled
G2&G3: Gi coupled
Function of pre-synaptic metabotropic receptors
control NT release
Function of post-synaptic metabotropic receptors
learning, memory, and motor systems
What happens in glial cell once EAA is taken up?
NO is released.
What also releases NO
Macrophages, can damage neurons
If neurons are ischemic for four minutes, what happens?
O2 goes to zero.
ATP decreases, Na/K Atpase decreases
Cell membrane depolarizes
Neuron reaches threshold, and AP occurs
What takes up EAA
based on secondary active transport of Na in glial cell
What happens after AP occurs during ischemic event
EAA is released into different parts of the brain
Calcium increases intracellularly
Releases arachidonic acid, and leads to Ca release from ER and mitochondria.
Unfolded protein response occurs, and Elf2a kinase activation occurs, leads to mitochondrial dysfunction.
mu calpain released, proteolysis of proteins.
What does u-calpain do
leads to metabolic and structural impairment of neurons
High intracellular calcium can also lead to activation of what protein
calcineurin
function of calcineurin
Excess production of NO from NOS
What is one of the final stages of an ischemic event
apoptotic pathway activated
Problem associated with reperfusion
O2 can’t be taken back up, turns into free radicals that continuously damages the cells.
O2 excess can lead to what
Free radicals, and phosphorylation of elF2a, which decreases protein synthesis even further. Increases apoptotic signaling.
