Glutamate and Anaesthesia Flashcards
How can we see the function of glutamate receptors in cell lines?
Typically you would transfect cells which do not express these receptors
And apply pulse of agonists
Use whole cell voltage clamp recordings of the cell
Can be done for AMPA, NMDAR and kainite too
Why does Mg2+ block the NMDAR?
Positive charge attracted to the negative membrane potential
What do NMDARs conduct?
Ca2+
K+ in the opposite direction
What can blockage of NMDAR cause?
Psychotic state
ie with ket and PCP
In addition to glutamate, what else does the NMDAR require to stay open?
A coagonist - glycine or D-serine
How do we know that NMDAR activation requires agonist and coagonist binding?
From whole cell voltage clamp recordings
Noted that in the absence of glycine, glutamate current is not persistent as it does not activate NMDARs
Where does glutamate bind to the NMDAR?
GluN2 subunit
Where does glycine bind to NMDAR?
GluN1 subunit
How do we know that Mg2+ blocks slow NMDAR transmission?
Measurement of NMDAR EPSCs in neurons
Cells in solutions containing Mg2+ only demonstrate a fast EPSC which is dampened by a AMPA antagonist (CNQX)
In Mg2+ free solution the EPSCs have a slow and a fast component
The CNQX here has no affect on the slow component
Which part of the glutamate receptor is the part which makes up the ion channel?
TM2
What are most GluA2 subunits edited to in an adult?
GluAR
GluAR is calcium impermeable
T/F
True
GluA1,3,4 and unedited GluA2(Q) are calcium permeable
What is the edit made in GluA2?
Adenosine to arginine in the TM2 re-entrant loop
Q607R
Why don’t polyvalent cations (such as spermine) block GluA2R?
It is positive so is repelled by the positive charge of arginine
What do AMPARs mediate?
Fast synaptic transmission