NT excitotoxicity

Question 1

The ionotropic ion receptor NMDA allows primarily what ion in?

Answer 1

Calcium

Question 2

What are the different modulatory sites of the NMDA receptor?

Answer 2

• Glycine binding site
• pH sensitive region
• Zinc-binding site
• PCP binding site
• magnesium binding site

Question 3

What is the effect of glycine on the NMDA receptor?

Answer 3

Co-agonist: potentiates the effects of the primary ligand

Question 4

What is the effect of the pH sensitive region on the NMDA receptor?

Answer 4

Increased hydrogen ion inhibits the opening of the channel

Question 5

Where is the zinc binding site on the NMDA receptor?

Answer 5

inside the cell

Question 6

What is the effect of the zinc binding site on the NMDA receptor?

Answer 6

modifies the calcium current into the cell

Question 7

Where in the PCP binding site of the NMDA receptor located?

Answer 7

Inside the cell and gate

Question 8

What is the effect of the PCP binding site on the NMDA receptor?

Answer 8

Drugs bind here and block the calcium current

Question 9

Where is the magnesium binding site on the NMDA receptor?

Answer 9

inside the cell

Question 10

What is the effect of the magnesium binding site on the NMDA receptor?

Answer 10

• Blocks the effects at physiological levels
• Mg is bound at resting membrane potentials
• With depolarization it leaves and allow Ca in

Question 11

What activates an AMPA receptor?

Answer 11

• Exogenous AMPA
• Glutamate
• Aspartate

Question 12

What is the effect of binding to a AMPA receptor?

Answer 12

primarily Na influx

Question 13

What are the 2 non NMDA receptors?

Answer 13

AMPA and Kainate

Question 14

What binds to and opens the Kainate receptor?

Answer 14

• Exogenous Kainate
• Glutamate
• Aspartate

Question 15

What ion is allowed in a Kainate receptor?

Answer 15

can be Ca but primarily Na

Question 16

What cells remove glutamate from the synapse?

Answer 16

Astrocytes

Question 17

How do astrocytes remove glutamate from the synapse?

Answer 17

Covert it to glutamine via glutamine synthetase

Question 18

What happens to the glutamine after astrocytes make it from glutamate?

Answer 18

the neurons take it back up and it is used as a second source of glutamate

Question 19

General function of the non NMDA receptors?

Answer 19

• Primary afferents in spinal

- General excitatory synaptic transmission

Question 20

what are the NMDA receptors involved in?

Answer 20

• producing long-term changes in synaptic strength via long term potentiation
• memory
• learning

Question 21

General effects of EAA’s at metabotropic receptors?

Answer 21

• decrease synaptic excitability

- long term effects

Question 22

Explain how NMDA activation leads to increase in NO

Answer 22

• Calcium influx by receptor activation leads to calcineurin activation
• Calcineurin is a phosphatase that cleaves a phosphate group from NOS thus activating it
• NOS then cleaves NO from arginine
• NO leaves the cell

Question 23

What does the NO induce in the cell?

Answer 23

activation of guanylyl cyclase and formation of cGMP

Question 24

How is NO removed from synapse?

Answer 24

• Has a half life of 5 seconds then degrades

- some proteins also bind to it (hemoglobin)

Question 25

In neurons, how long after ischemia is there zero ATP?

Answer 25

4 minutes

Question 26

during an ischemic event, when calcium enters the cell, what enzymes does it activate?

Answer 26

• phospholipase A
• calcinuerin
• mu-calpain