Glutamatergic physiology Flashcards
nearly all CNS drugs produce their therapeutic effects by …….. ?
modifying certain steps in neurotransmission
what is the main excitatory neurotransmitter?
glutamate
how much glutamate synapses are there in the CNS?
50%
what are the steps/properties for glutamate metabolism?
synthesis
storage
release
deactivation
what is the precursor for glutamate?
alpha-ketoglutarate
what enzyme converts alpha-keto to glutamate?
GABA-transaminase aka GABA-T
what is H+-ATPase?
it is a primary active transporter that generate a proton gradient inside the vesicle
what is the proton gradient used for?
to transport glutamate inside the vesicle
what transporter transport glutamate into the vesicle?
VGLUT; an antiport
using the proton gradient to transport glutamate inside and proton outside simultaneously
what starts the process of glutamate release?
an action potential generated and reach the cell membrane
what happens after an action potential is generated?
an influx of Ca2+ into the nerve cell, increasing the cytosolic Ca2+, causing the movement of the vesicle towards the membrane
what are the two ways glutamate can be deactivated?
by re-uptake into the presynaptic nerve terminal by Gt(n) transporter
by uptake into glial cells by glial Gt(g) transporter
what does uptake into glial cell provide?
an additional source for glutamate release
what happens after glutamate is uptake into glial cells?
glutamate –> glutamine by enzyme glutamine synthetase
glutamine transferred to presynaptic terminal by glutamine transporters
glutamine —> glutamate by enzyme mitochondria-associated glutaminase
what are the two types of glutamate receptors?
ionotropic receptors
metabotropbic receptors
what are ionotropic receptors?
ligand-gated ion channels
permeable for Ca, Na, and K ions
what are metabotropic receptors?
GPCR receptors
what are the 3 ionotropic subtype receptors?
AMPA
kainate
NMDA
what kind of response are ionotropic?
fast and excitatorye
what kind of response is metabotropic?
slow response
what can block NMDA receptors?
Mg2+
how can NMDA block be removed?
needs a membrane depolarization to remove Mg2+ block
where are AMPA-r located?
thru out CNS, mainly hippocampus and cerebral cortex
what are the agonist for AMPA-r?
glutamate
AMPA