Excitatory amino acids and excitotoxicity Flashcards Preview

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Flashcards in Excitatory amino acids and excitotoxicity Deck (36)
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1
Q

glutamate comes from what

A

alpha-ketoglutarate

2
Q

the metabolic and NT pools of glutamate are/are not strictly separated

A

are

3
Q

aspartate comes from ___

- where is it the NT

A

oxaloacetate

visual cortex and pyramidal cells

4
Q

what is the excitatory ionotropic receptor

A

NMDA receptor

5
Q

what is the effect of NMDA receptor binding

A

allows Ca++ influx

6
Q

glycine binding site

A

co-agonist
presence of glycine required for EAA to have effect
-on own cannot open channel

7
Q

magnessium binding site on NMDA

A

inside channel
blocks channel, prevents influx of calium
-cell must open and depolarize in order for magnesium to be repelled out

8
Q

3 modulator sites onf NMDA channel

A

glycine
mg++
PCP

9
Q

PCP binding site

A

inside channel, deep to Mg++
blocks channel
no calcium allowed in
irreversible binding

10
Q

NMDA receptor activation leads to what

what kind of onset and duration

A

EPSP
slow onset bc of process, getting magneium out
prolonged duration bc calcium is entering, it is bigger and slower

11
Q

non-NMDA receptor influx

-2 subtypes

A

sodium influx (some: very small amount of calcium too)

AMPA
kainate

12
Q

what inhibits the AMPA response to EAA

A

benzodiazepine

13
Q

why is it important to have NMDA and non-NMDA receptors at the same post synaptic membrane

A

need to have sodium influx from non-NMDA to depolarize cell and allow for the sodium to repel Mg++ on the NMDA receptor so that calcium can rush in

14
Q

which non-NMDA receptor allows a little bit of calcium into the cell as well as sodium

A

kainate

15
Q

where is the NMDA receptor located

A

almost exclusively post synaptically

16
Q

where is the location of metabotropic receptors for EAA

A

both pre and post synaptically

pre control release of NT

17
Q

function of non-NMDA receptors

A

primary afferents

premotor (upper mn)

18
Q

function of NMDA receptors

A

long term changes in synaptic strength
learning
memory

19
Q

getting rid of the EAA: neurons and glia

A

2ndary active transport with sodium

-high affinity

20
Q

getting rid of EAA: glia

A

convert glutamate to glutamine and release into ECF

-neurons take glutamine up and convert it back to gluatamate

21
Q

when calcium influxes into cell from NMDA receptor opening what does it bind and what does this activate

A

binds calcineurin and activates NOS

-arginine–>NO

22
Q

NO is ___ soluble and can work where

A

lipid

pre and post synaptic cells and also on neighboring cells

23
Q

Neural functions of NO

A

long-term potentiation and memory

cardiovascular and respiratory control

24
Q

how is NO toxic and what cells affected

A

can create free radicals
-cells that make NO have protective mechanisms against it but neighboring cells can be damaged bc they don’t have protection

25
Q

EAA (glut/asp/taurine

Central location
function 
ITR
MTR
other
A

central location: widespread spinal cord through cortex
fnct: primary afferents, motor activation of a-motor neuron
-soncsciousness, learning, memory
ITR: NMDA and Non-NMDA
MTR: yes
other: NOS activation and NO production

26
Q

what happens in the area most directly affected by ischemia

A

anoxic core
oxygen deprivation
cells unable to meet metabolic needs
-depolarization of the membrane (Na+/K+ pump shuts down)
-causes APs to be released and NTs cause activation of receptors of whereever they synapse

27
Q

high levels of EAA effect

A

EAA release is excessive, EAA re-uptake is Na+ dependent so not working
-NMDA receptor is activated = calcium influx

28
Q

what does an increased in Ca++ initiate

A

activation of phospholipase A2
activation of calcineurin (phosphatase)
activation of mu-calpain (protease)
activation of apoptotic pathway

CAMP

29
Q

excessive activation of phospholipase A2 effect

A

too much arachidonate acid release from membrane, causes physical damage

  • arachidonate acts at ryanodine receptor on ER increases calcium even more
  • unfolded protein response- stops making protein
  • activation of eIF2a-kinase
  • mitochondria impaired function
30
Q

activation of u-caplpain (protease)

A

proteolysis: chews up existing proteins, damages neurons that weren’t hypoxic enough to die
- spectrin chewed up (structural damage)
- eIF4G chewed up (needed for protein synthesis)

31
Q

activation of calcineurin

A

phosphatase

increases NO synthesis which becomes elevated to a toxic level

32
Q

apoptotic pathway

A

disruption of mitochond and ER function increases free cytosolic calcium
-cytochrome C leaks, activates caspase 9 which activates caspase 3 (proteolytic enzyme, apoptotic)

33
Q

reperfusion injury

A

when give blood and oxygen back to damaged area much of the O2 wil end up as a free radical bc damaged neurons no longer utilize oxygen correctly = radical

34
Q

mitochondria that can make ATP in hypoxic cells

___ phosphorylation leads to apoptosis

A

make ATP, kinases take ATP and phosphorylate things that you do not want phosphorylated
-eIF2a kinase phosphorylation leads to decrease in protein syn and activates caspase 3 —>apoptosis

35
Q

in high quantity NO contributes to edema by

A

damaging capillary endothelial cells

36
Q

how do you treat excitotoxicity

A

try to stop NMDA receptors

-PCP?? i want some