Karius- EAA System & Excitotoxicity Flashcards
2 main EAAs?
glutamate and aspartate
where is aspartate used as NT?
visual cortex and pyramidal cells
what are the ionotropic EAA receptors?
NMDA and non-NMDA
what do NMDA receptors allow in?
Calcium
what is required as a co-agonist for glutamate on NMDA?
glycine
What are the 2 modulatory sites on NMDA receptors?
magnesium site and PCP
what must happen to remove Mg from NMDA receptor?
slight depolarization
what does the epsp look like for NMDA receptors?
slow onset and prolonged duration
non-NMDA receptors allow what ion in?
Na
what are the 2 kinds of non-NMDA receptors?
AMPA and Kainate
what is unique about AMPA receptor?
benzo site- inhibits response to NT
Kainate is the simplest receptor because?
no modification sites, activated by either EAA or Kainate
what does kainate allow in?
some Ca with Na
what do non-NMDA receptor epsp look like?
typical action potential
where are non-NMDA receptors normally found?
with NMDA receptors
where are metabotropic receptors found?
pre and post synaptic (pre= NT release feedback, not necessarily neg.)
non-NMDA receptors are found?
primary afferents (direct sensory from periphery to CNS) pre-motor (from cortex to alpha(upper) motor neurons)
how are EAAs limited?
neurons and glia uptake system
how do neurons and glial cells uptake EAAs?
Secondary Sodium activity
what do glial cells do with glutamate?
turn it into glutamine and release it into ECF, neurons take this back up and convert back to glutamate
Calcium that comes in the NMDA receptors bind to what?
calcineurin
what does calcineurin activate?
NO synthase
what is NO used for?
long-term potentiation and memory, CV/respiratory control
what can NO do to neurons?
can be toxic d/t free radicals that can kill neurons and bacteria
If there’s an ischemic event what can this cause? (mechanism of excitotoxicity)
O2 deprivation, cell depolarization, EAA release
what channel doesn’t work that causes cells to depolarize?
Na/K channel
what else is activated by increase in Ca2?
phospholipase A2
what does PLA2 do?
damages membrane, acts on receptors, Ca2 from intracell. stores=> unfolded protein response, activation of eIF2alpha- kinase=> mito impaired fxn
activation of mu-calpain does what?
proteolysis and activation of spectrin and eIF4G
what does NOS cause in mito membranes?
disruption leading to activation of apoptotic pathways
what are the 2 things that activate apoptotic pathway to caspase 3?
cytochrome C + caspase 9
what is the danger of reperfusion of damaged neurons?
enzymes not normal, O2 becomes free radical
what does phosphorylation of eIF2alpha kinase lead to?
decrease in protein synthesis and activates caspase 3
how soon does the apoptotic cascade start after event?
4 mins
