Excitatory amino acids and excitotoxicity Flashcards Preview

Neuroscience 1 > Excitatory amino acids and excitotoxicity > Flashcards

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

glutamate comes from what

alpha-ketoglutarate

2

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

are

3

aspartate comes from ___
- where is it the NT

oxaloacetate
visual cortex and pyramidal cells

4

what is the excitatory ionotropic receptor

NMDA receptor

5

what is the effect of NMDA receptor binding

allows Ca++ influx

6

glycine binding site

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

7

magnessium binding site on NMDA

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

8

3 modulator sites onf NMDA channel

glycine
mg++
PCP

9

PCP binding site

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

10

NMDA receptor activation leads to what
what kind of onset and duration

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

11

non-NMDA receptor influx
-2 subtypes

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

AMPA
kainate

12

what inhibits the AMPA response to EAA

benzodiazepine

13

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

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

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

kainate

15

where is the NMDA receptor located

almost exclusively post synaptically

16

where is the location of metabotropic receptors for EAA

both pre and post synaptically
pre control release of NT

17

function of non-NMDA receptors

primary afferents
premotor (upper mn)

18

function of NMDA receptors

long term changes in synaptic strength
learning
memory

19

getting rid of the EAA: neurons and glia

2ndary active transport with sodium
-high affinity

20

getting rid of EAA: glia

convert glutamate to glutamine and release into ECF
-neurons take glutamine up and convert it back to gluatamate

21

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

binds calcineurin and activates NOS
-arginine-->NO

22

NO is ___ soluble and can work where

lipid
pre and post synaptic cells and also on neighboring cells

23

Neural functions of NO

long-term potentiation and memory
cardiovascular and respiratory control

24

how is NO toxic and what cells affected

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

EAA (glut/asp/taurine

Central location
function
ITR
MTR
other

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

what happens in the area most directly affected by ischemia

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

high levels of EAA effect

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

28

what does an increased in Ca++ initiate

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

CAMP

29

excessive activation of phospholipase A2 effect

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

activation of u-caplpain (protease)

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

activation of calcineurin

phosphatase
increases NO synthesis which becomes elevated to a toxic level

32

apoptotic pathway

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

33

reperfusion injury

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

mitochondria that can make ATP in hypoxic cells
___ phosphorylation leads to apoptosis

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

in high quantity NO contributes to edema by

damaging capillary endothelial cells

36

how do you treat excitotoxicity

try to stop NMDA receptors
-PCP?? i want some