Signalling Flashcards
What receptors are there for Glutamate?
ionotropic and metabotropic
what is glutamate?
main excitatory neurotransmitter in the BRAIN
released in half of the neurones
non-essential amino acid
where is glutamate synthesised?
synthesised locally in the brain as can’t cross the BBB
what are glutamates action?!
calcium influx = causing action potential
role in plastic changes with memory, learning, and development
what are glutamate’s ionotropic receptors?
AMPA
NMDA - requires glycine co-agonist
kainate
What is NMDAs purpose?
calcium influx related to synaptic plasticity in memory and learning - NMDA is opened with a high increase in EPSPs - unblocks in LTP
What is AMPAs purpose?
plasticity and synaptic transmission
in LTP more of these are inputted in post synaptic membrane
What happens when there’s too much Glutamate?
excessive influx of Ca2+ which can lead to cell death
what cell pathways are effected in glutamate excitotoxicity?
- membrane breakdown (phospholipase)
- cytoskeleton alteration
- generation of nitrogen oxide free radicals
If GluR2 is non-editing in an adult what disease may it imply?
MND
What is Glutamates PD pathology?
- balance between NMDA excitation and D2 inhibition
- in PD loss of D2 results in over-activation of glutamate receptors (plastic changes)
- causes excitotoxicity in PD
What does activation of NMDA receptors enhance in AD?
Production of amyloid beta plaques and phosphorylates tau
What pharmacological evidence is there for glutamate mediated damage in AD?
memantine (NMDA antagonist) leads to functional improvement in AD
What is the distribution of muscarinic recpetors?
midbrain, medulla and pons
What is the distribution of nicotinic receptors?
sub nig, locus coerleus, septum