EAA and Excitotoxicity

Question 1

What three things are vital to normal brain function

Answer 1

calcium, oxygen, EAA

Question 2

What are the EAAs

Answer 2

Glu, Asp

Question 3

Where does Asp typically work

Answer 3

Serves as neurotransmitter in visual cortex and pyramidal cells

Question 4

What receptors are receptive to EAA

Answer 4

NMDA and non-NMDA

Question 5

Function of NMDA

Answer 5

Influx of calcium

Question 6

What is one of the binding sites in NMDA

Answer 6

Glycine binding site, specifically, with another EAA

Question 7

What type of receptor is NMDA

Answer 7

Ionotropic

Question 8

Where is the Mg binding site in NMDA

Answer 8

within channel itself, and blocks the channel

Question 9

Function of Mg in channel

Answer 9

prevents calcium influx when channel is open, makes NMDA receptor both ligand and voltage gated

Question 10

Where is the PCP binding site

Answer 10

In channel, beneath Mg

Question 11

Function of PCP

Answer 11

Horse tranquilizer, blocks channel

Question 12

non-NDMA function

Answer 12

primarily a Na influx

Question 13

what type of receptor is non-NMDA

Answer 13

ionotropic

Question 14

What are the types of non-NMDA receptors

Answer 14

AMPA and Kainate

Question 15

What can bind to AMPA

Answer 15

EAA and Benzodiazepines

Question 16

Function of AMPA

Answer 16

Na influx, when benzodiazepines bind it reduces the amount of Na that enters

Question 17

What type of potential is formed by non-NMDA

Answer 17

typical excitatory post synaptic potential, relatively short onset and duration

Question 18

What type of potential is formed by NMDA

Answer 18

long latency epsp with a long duration

Question 19

Function of non-NMDA and NMDA together

Answer 19

non-NDMA opens first, Na flows in and depolarizes. typical epsp forms, causes enough depolarization to cause the Mg to leave NMDA channel, Ca then comes in and forms lasting epsp.

Question 20

Functions of non-NMDA

Answer 20

primary sensory afferents, upper motorneurons

Question 21

Function of NMDA receptors

Answer 21

critical in short and long term memory formation, synaptic plasticity

Question 22

What types of EAA metabotropic receptors exist

Answer 22

G1: Gq coupled

G2&G3: Gi coupled

Question 23

Function of pre-synaptic metabotropic receptors

Answer 23

control NT release

Question 24

Function of post-synaptic metabotropic receptors

Answer 24

learning, memory, and motor systems

Question 25

What happens in glial cell once EAA is taken up?

Answer 25

NO is released.

Question 26

What also releases NO

Answer 26

Macrophages, can damage neurons

Question 27

If neurons are ischemic for four minutes, what happens?

Answer 27

O2 goes to zero.
ATP decreases, Na/K Atpase decreases
Cell membrane depolarizes
Neuron reaches threshold, and AP occurs

Question 28

What takes up EAA

Answer 28

based on secondary active transport of Na in glial cell

Question 29

What happens after AP occurs during ischemic event

Answer 29

EAA is released into different parts of the brain
Calcium increases intracellularly
Releases arachidonic acid, and leads to Ca release from ER and mitochondria.
Unfolded protein response occurs, and Elf2a kinase activation occurs, leads to mitochondrial dysfunction.
mu calpain released, proteolysis of proteins.

Question 30

What does u-calpain do

Answer 30

leads to metabolic and structural impairment of neurons

Question 31

High intracellular calcium can also lead to activation of what protein

Answer 31

calcineurin

Question 32

function of calcineurin

Answer 32

Excess production of NO from NOS

Question 33

What is one of the final stages of an ischemic event

Answer 33

apoptotic pathway activated

Question 34

Problem associated with reperfusion

Answer 34

O2 can’t be taken back up, turns into free radicals that continuously damages the cells.

Question 35

O2 excess can lead to what

Answer 35

Free radicals, and phosphorylation of elF2a, which decreases protein synthesis even further. Increases apoptotic signaling.