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
where are both muscarinic & nicotinic?
putamen caudate cortex hippocampus thalamus hypothalamus cerebellum
How is ACh used in the sympathetic nervous system?
preganglionic (nicotinic)
How is ACh used in the parasympathetic nervous system?
pre (nicotinic) and post ganglionic (muscarinic)
What are the 2 types of ACh receptors?
Nicotinic - ionotropic
Muscarinic - metabotropic
What is the pathophysiology of Mysthenia Gravis?
- Autoimmune
- autoantibodies against nicotinic ACh receptors on the post synaptic membrane of the NMJ
- error in transmission of signal from neurone to muscle cell
- Muscle can’t contract
Name 3 possible affected proteins in MG.
Nicotinnic ACh Receptors
MUSK - muscle specific kinase
lipoprotein related protein 4
How does nerve agent cause damage?
blocks activity of acetylcholinesterase
causing accumulation in the synaptic cleft
=chronic depolarisation
What symptoms would be expected from Acetylcholinesterase inhibitors (over activation of acetlycholine) ?
SLUDGEM
salivation, lacrimation, urination, defecation, Gastro pain, emesis, miosis.
3 drugs that treat opioid poisoning + there action.
atropine - antagonist of muscarinic
diazepam - reduces release of Ach
pralidoxime - reactivation of AchE
