Glutamate Flashcards
How many subunits do ionotropic glutamate receptors have?
4 - are all tetrameric
What is the structure of ionotropic glutamate receptors?
- Large extracellular N terminal
- Intracellular carboxyl tail
- Re-entrant loop (Q/R site for AMPARs)
- Mostly heteromers, but homomers do exist
Where do glycine and glutamate bind on the NMDAR?
Glycine: GluN1
Glutamate: GluN2
Re-entrant loop on NMDARs?
Have N residue (asparagine) - site of magnesium block
Forms cation conducting ion channel
What receptors does ketamine activate?
Little effect on GABAARs
Inhibits NMDARs (is a use-dependent, voltage-dependent blocker of the ion channel - blocks for much longer than Mg2+ and attracted by negative membrane potential)
Which receptors are inhibitory (2) and which are excitatory (5) in the brain?
Inhibitory: GABAA, glycine
Excitation: AMPA, KAR, NMDA, alpha4beta2 nicotinic, 5HT3
What does IV ketamine do?
Induces dissociative anaesthetic state
Marked sensory loss, amnesia, analgesia, no complete loss of consciousness
Structurally related to PCP
May cause hallucinations
How quickly does ketamine work as an antidepressant?
Within 30 minutes
Effective in 1/3 of treatment resistant depression cases
What is laughing gas?
Synthesised by Joseph Priestley 1772
Nitrous oxide
Colourless + odourless gas
Used initially for tooth extractions
Non-competitive NMDAR antagonist
Rapid onset + offset of anaesthesia
Occasionally used as inhalation anaesthetic + analgesic durin short/painful procedures ie labour + dentistry
What is xenon?
Colourless + odourless gas
Rapid induction, short duration, lack of cardiovacular effects, powerful analgesic, neuroprotective effects
Non-competitive NMDA receptor anatgonist - inhibits glycine binding site on GluA1
Examples of NMDAR antagonists (3)
Nitrous oxide, xenon, ketamine
All have little to no effect on GABAARs
