Karius- EAA System & Excitotoxicity

Question 1

2 main EAAs?

Answer 1

glutamate and aspartate

Question 2

where is aspartate used as NT?

Answer 2

visual cortex and pyramidal cells

Question 3

what are the ionotropic EAA receptors?

Answer 3

NMDA and non-NMDA

Question 4

what do NMDA receptors allow in?

Answer 4

Calcium

Question 5

what is required as a co-agonist for glutamate on NMDA?

Answer 5

glycine

Question 6

What are the 2 modulatory sites on NMDA receptors?

Answer 6

magnesium site and PCP

Question 7

what must happen to remove Mg from NMDA receptor?

Answer 7

slight depolarization

Question 8

what does the epsp look like for NMDA receptors?

Answer 8

slow onset and prolonged duration

Question 9

non-NMDA receptors allow what ion in?

Answer 9

Na

Question 10

what are the 2 kinds of non-NMDA receptors?

Answer 10

AMPA and Kainate

Question 11

what is unique about AMPA receptor?

Answer 11

benzo site- inhibits response to NT

Question 12

Kainate is the simplest receptor because?

Answer 12

no modification sites, activated by either EAA or Kainate

Question 13

what does kainate allow in?

Answer 13

some Ca with Na

Question 14

what do non-NMDA receptor epsp look like?

Answer 14

typical action potential

Question 15

where are non-NMDA receptors normally found?

Answer 15

with NMDA receptors

Question 16

where are metabotropic receptors found?

Answer 16

pre and post synaptic (pre= NT release feedback, not necessarily neg.)

Question 17

non-NMDA receptors are found?

Answer 17

primary afferents (direct sensory from periphery to CNS)
pre-motor (from cortex to alpha(upper) motor neurons)

Question 18

how are EAAs limited?

Answer 18

neurons and glia uptake system

Question 19

how do neurons and glial cells uptake EAAs?

Answer 19

Secondary Sodium activity

Question 20

what do glial cells do with glutamate?

Answer 20

turn it into glutamine and release it into ECF, neurons take this back up and convert back to glutamate

Question 21

Calcium that comes in the NMDA receptors bind to what?

Answer 21

calcineurin

Question 22

what does calcineurin activate?

Answer 22

NO synthase

Question 23

what is NO used for?

Answer 23

long-term potentiation and memory, CV/respiratory control

Question 24

what can NO do to neurons?

Answer 24

can be toxic d/t free radicals that can kill neurons and bacteria

Question 25

If there’s an ischemic event what can this cause? (mechanism of excitotoxicity)

Answer 25

O2 deprivation, cell depolarization, EAA release

Question 26

what channel doesn’t work that causes cells to depolarize?

Answer 26

Na/K channel

Question 27

what else is activated by increase in Ca2?

Answer 27

phospholipase A2

Question 28

what does PLA2 do?

Answer 28

damages membrane, acts on receptors, Ca2 from intracell. stores=> unfolded protein response, activation of eIF2alpha- kinase=> mito impaired fxn

Question 29

activation of mu-calpain does what?

Answer 29

proteolysis and activation of spectrin and eIF4G

Question 30

what does NOS cause in mito membranes?

Answer 30

disruption leading to activation of apoptotic pathways

Question 31

what are the 2 things that activate apoptotic pathway to caspase 3?

Answer 31

cytochrome C + caspase 9

Question 32

what is the danger of reperfusion of damaged neurons?

Answer 32

enzymes not normal, O2 becomes free radical

Question 33

what does phosphorylation of eIF2alpha kinase lead to?

Answer 33

decrease in protein synthesis and activates caspase 3

Question 34

how soon does the apoptotic cascade start after event?

Answer 34

4 mins