Excitatory amino acids and excitotoxicity

Question 1

glutamate comes from what

Answer 1

alpha-ketoglutarate

Question 2

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

Answer 2

are

Question 3

aspartate comes from ___

- where is it the NT

Answer 3

oxaloacetate

visual cortex and pyramidal cells

Question 4

what is the excitatory ionotropic receptor

Answer 4

NMDA receptor

Question 5

what is the effect of NMDA receptor binding

Answer 5

allows Ca++ influx

Question 6

glycine binding site

Answer 6

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

Question 7

magnessium binding site on NMDA

Answer 7

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

Question 8

3 modulator sites onf NMDA channel

Answer 8

glycine
mg++
PCP

Question 9

PCP binding site

Answer 9

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

Question 10

NMDA receptor activation leads to what

what kind of onset and duration

Answer 10

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

Question 11

non-NMDA receptor influx

-2 subtypes

Answer 11

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

AMPA
kainate

Question 12

what inhibits the AMPA response to EAA

Answer 12

benzodiazepine

Question 13

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

Answer 13

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

Question 14

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

Answer 14

kainate

Question 15

where is the NMDA receptor located

Answer 15

almost exclusively post synaptically

Question 16

where is the location of metabotropic receptors for EAA

Answer 16

both pre and post synaptically

pre control release of NT

Question 17

function of non-NMDA receptors

Answer 17

primary afferents

premotor (upper mn)

Question 18

function of NMDA receptors

Answer 18

long term changes in synaptic strength
learning
memory

Question 19

getting rid of the EAA: neurons and glia

Answer 19

2ndary active transport with sodium

-high affinity

Question 20

getting rid of EAA: glia

Answer 20

convert glutamate to glutamine and release into ECF

-neurons take glutamine up and convert it back to gluatamate

Question 21

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

Answer 21

binds calcineurin and activates NOS

-arginine–>NO

Question 22

NO is ___ soluble and can work where

Answer 22

lipid

pre and post synaptic cells and also on neighboring cells

Question 23

Neural functions of NO

Answer 23

long-term potentiation and memory

cardiovascular and respiratory control

Question 24

how is NO toxic and what cells affected

Answer 24

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

Question 25

EAA (glut/asp/taurine ``` Central location function ITR MTR other ```

Answer 25

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

Question 26

what happens in the area most directly affected by ischemia

Answer 26

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

Question 27

high levels of EAA effect

Answer 27

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

Question 28

what does an increased in Ca++ initiate

Answer 28

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

Question 29

excessive activation of phospholipase A2 effect

Answer 29

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

Question 30

activation of u-caplpain (protease)

Answer 30

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)

Question 31

activation of calcineurin

Answer 31

phosphatase | increases NO synthesis which becomes elevated to a toxic level

Question 32

apoptotic pathway

Answer 32

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

Question 33

reperfusion injury

Answer 33

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

Question 34

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

Answer 34

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

Question 35

in high quantity NO contributes to edema by

Answer 35

damaging capillary endothelial cells

Question 36

how do you treat excitotoxicity

Answer 36

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