NT excitotoxicity Flashcards
The ionotropic ion receptor NMDA allows primarily what ion in?
Calcium
What are the different modulatory sites of the NMDA receptor?
- Glycine binding site
- pH sensitive region
- Zinc-binding site
- PCP binding site
- magnesium binding site
What is the effect of glycine on the NMDA receptor?
Co-agonist: potentiates the effects of the primary ligand
What is the effect of the pH sensitive region on the NMDA receptor?
Increased hydrogen ion inhibits the opening of the channel
Where is the zinc binding site on the NMDA receptor?
inside the cell
What is the effect of the zinc binding site on the NMDA receptor?
modifies the calcium current into the cell
Where in the PCP binding site of the NMDA receptor located?
Inside the cell and gate
What is the effect of the PCP binding site on the NMDA receptor?
Drugs bind here and block the calcium current
Where is the magnesium binding site on the NMDA receptor?
inside the cell
What is the effect of the magnesium binding site on the NMDA receptor?
- Blocks the effects at physiological levels
- Mg is bound at resting membrane potentials
- With depolarization it leaves and allow Ca in
What activates an AMPA receptor?
- Exogenous AMPA
- Glutamate
- Aspartate
What is the effect of binding to a AMPA receptor?
primarily Na influx
What are the 2 non NMDA receptors?
AMPA and Kainate
What binds to and opens the Kainate receptor?
- Exogenous Kainate
- Glutamate
- Aspartate
What ion is allowed in a Kainate receptor?
can be Ca but primarily Na
What cells remove glutamate from the synapse?
Astrocytes
How do astrocytes remove glutamate from the synapse?
Covert it to glutamine via glutamine synthetase
What happens to the glutamine after astrocytes make it from glutamate?
the neurons take it back up and it is used as a second source of glutamate
General function of the non NMDA receptors?
- Primary afferents in spinal
- General excitatory synaptic transmission
what are the NMDA receptors involved in?
- producing long-term changes in synaptic strength via long term potentiation
- memory
- learning
General effects of EAA’s at metabotropic receptors?
- decrease synaptic excitability
- long term effects
Explain how NMDA activation leads to increase in NO
- 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
What does the NO induce in the cell?
activation of guanylyl cyclase and formation of cGMP
How is NO removed from synapse?
- Has a half life of 5 seconds then degrades
- some proteins also bind to it (hemoglobin)
In neurons, how long after ischemia is there zero ATP?
4 minutes
during an ischemic event, when calcium enters the cell, what enzymes does it activate?
- phospholipase A
- calcinuerin
- mu-calpain
