EAA and Excitoxicity Flashcards
Where does aspartate serve as a neurotransmitter?
visual cortex and pyramidal cells
What are the receptor types for EAA?
ionotropic and metabotropic
several kinds of each
What is the NMDA receptor?
EAAs activate it –> influx of calcium
has multiple modulatory sites - glycine binding site
How does glycine affect the NMDA receptor?
required co-agonist, but it alone cannot open the channel
both EAA and glycine must be present for the channel to open
How does magnesium affect the NMDA receptor?
within the channel itself
blocks the channel at resting membrane potential
prevents Ca influx when the channel opens
makes the receptor both ligand and voltage-gated
How does PCP affect the NMDA receptor?
blocks channel
What are the 2 main types of non-NMDA receptors for EAA?
AMPA
Kainate
What is AMPA?
non-NMDA receptor for EAA
ionotropic - primarily Na influx
glutamate/aspartate are the endogenous ligands
What is the main regulatory site for AMPA?
benzodiazepines bind site on extracellular face of protein
reduce the amt of sodium that enters
What is the difference in excitation from activation of non-NMDA and NMDA receptors?
non-NMDA: typical excitatory post-synaptic potential (epsp)
NMDA: long latency epsp w/ long duration
Why does NMDA receptor have a longer latency epsp?
non-nmda receptor act –> typical epsp –> depolarization can cause Mg to leave NMDA channel –> Ca now enters NMDA channel –> longer lasting epsp
What is the relationship based on location of non-NMDA and NMDA receptors?
non-NMDA receptors do not exist on post-synaptic membranes w/out NMDA receptors
in some systems
What are the functions of EAA receptors?
non-nmda: primary sensory afferents, upper motoneurons, others
nmda: critical in short and long-term memory formation, synaptic plasticity
What are the main groups of metabotropic EAA receptors and what is their GPCR type?
group 1: Gq
Groups 2 and 3: Gi
Where are EAA metabotropic receptors and what do they function in?
pre-synaptic: control NT release
post-synaptic: learning, memory, motor systems
How are EAAs broken down and how does this limit EAA actions?
glial cells surrounding synapses absorb EAA –> breakdown to glutamine = inactive
glutamine uptaken to presyn neuron and recycled to EAA
How are NMDA receptors and nitric oxide related?
EAA binds NMDA –> Ca influx –> binds calcineurin
NOS triggered to convert Arginine to NO
Influx of what ion is likely to cause an inhibitory post-syn potential (ipsp)?
chloride
What type of NT is glycine typically?
inhibitory
What is the main effect of EAA at NMDA receptors?
producing long-term changes in synaptic strength via a process known as long term potentiation
memory
learning
Which receptor is thought to be used with EAA for synaptic plasticity assoc w/ learning?
metabotropic receptors
What are the general effects of NO outside CNS?
increases cGMP in endothelial cells –> causes sm m relaxation
major inhibitory NT in gut –> relaxation
immune: free radial in macrophages to kill bacteria
What are the CNS effects of NO?
long term potentiation of presyn neuron (respiratory control, cardio control, memory/learning)
*major control of cerebral vasculature –> dilation
How is NO removed from a synapse?
no uptake system for NO as it is lipid soluble
half-life of 5 seconds and then it degrades
some proteins do bind it
