CNS 4 Flashcards
what is glutamate?
most abundant amino acid
is intermediate in neuronal metabolism (precursor for GABA)
what does glutamate act as?
major excitatory neurotransmitter in brain
glutamate is synthesised in the nerve terminals from 2 sources
what are these?
- from glucose via Krebs cycle
- from glutamine by enzyme glutamine
glutamine is synthesised by glia cells + taken up by neurones
where is Glu stored?
vesicles + released by ca2+ dependent mechanism
how is Glu removed?
from synapse by high affinity reuptake into nerve terminals + neighbouring glial cells
the action of glutamate is not stopped by…
enzymatic breakdown
what is the action of glutamate stopped by?
2 transport pumps (Na+/K+ coupled glutamate transporters)
where are the Na+/K+ coupled glutamate transporters located?
- first pumps in pre-sn
- second pumps in nearby glia cells
glutamate taken up by …. is converted to glutamine
astroglial cells
what is glutamine inactive in the sense?
it cannot activate glutamate receptors
it is released from glial cells into extracellular fluid
what does glutamate act at?
3 different types of ionotropic receptors + at family at G protein coupled receptors
describe the binding at ionotropic receptors?
- NMDA receptors bind glutamate + NMDA
- AMPA receptors bind glutamate, AMPA and quisqualic acid
- kainate receptors bind glutamate + kainic acid
what are metabotropic glutamate receptors (mGluRs)?
members of G protein coupled receptor (GPCR) superfamily
most abundant receptor gene family in human genome
what do mGluRs mediate?
slow synaptic glutamate response by coupling to second messenger cascades + ion channels via heterotrimeric G proteins
what are mGluRs linked to?
second messenger systems
lead to inc of intracellular ca2+ / dec of cAMP
when mGluRs bind glutamate, what neurotransmitter do they create?
excitatory
what members of the G protein coupled receptor family are mGluRs part of?
group C
what do group I mGluRs couple to?
Gq/G11
- activate phospholipase C
- leads to hydrolysis of - phosphotinositides
- generation of IP3 + DAG
what do group II and III mGluRs couple to?
Gi/o
- inhibit adenylyl cyclase
- regulate ion channels + downstream signalling pathways
what are glutamatergic neurones and NMDA receptors in the hippocampus important in?
creation of LTP (long term potentiation)
—> memory
research studies show that the glutamate synapse is a potential target for wide range of neurological + psychiatric disorders.
give examples of these?
- epilepsy
- pain
- anxiety
- amnesia
what is gamma-aminobutyric acid (GABA)?
amino acid with high conc in brain + spinal cord
GABA is the most…
prevalent inhibitory neurotransmitter in CNS
in the spinal cord, about half of inhibitory neurones use what instead?
glycine
