Amino Acid Transmitters Flashcards
list the main three amino acid transmitters and the CNS and state whether they are inhibitory or excitatory
1) glutamate - excitatory
2) GABA - inhibitory
3) glycine - inhibitory
through which two types of receptors do glutamate and gaba regulate their effects
ion channels (ionotropic) and g protein coupled receptors (metabotropic)
where is glutamate synthesised? what are the two mechanisms of synthesis
the brain
1) synthesised from glutamine (from astrocytes) to glutamate by glutaminase
2) glucose metabolism
how is glutamate stored?
stored in synaptic vesicles.
H+ conc higher in vesicle than in cytoplasm. outflow of H+ allows transport of glutamate into vesicle
what is the mechanism of synaptic release of glutamate
the same as for ACh
how is glutamate mainly removed from the synaptic cleft
glutamate transporters on astrocytes.
1) co-transport of (2/3 Na)/H and glutamate
2) exchanging K+ for glutamate
name 3 ionotropic glutamate receptors
NMDA, AMPA, Kainate
how many polypeptide subunits make up one ionotropic glutamate receptor
4, they are clustered together to form a cylinder with a pore
where is the binding site on the glutamate ionotropic receptors
outside, near the N terminus
what ions are ampa receptors permeable to
Na and K
what ions are NMDA receptors permeable to
Na, K and Ca
what ions are kainate receptors permeable to
Na
binding of glutamate to AMPA and NMDA receptors causes what type of post synaptic potential
Excitatory post synaptic potential (they depolarise the cell)
which other amino acid needs to bind to NMDA receptors for them to function
glycine
how many types of metabotropic glutamate receptors are there and how many groups are there
8, grouped in 3 groups
where are metabotropic glutamate channels found on neurons
presynaptic and postsynaptic terminals
what happens to a g protein once glutamate has bound a metabotropic receptor
gdp is exchanged for gtp on alpha unit.
alpha unit dissociates from beta/gamma heteromer
activates intracellular proteins
what intracellular effects are observed when glutamate binds to type I metabotropic receptors
activated alpha subunit causes activation of phospholipase C, creates IP3/DAG
IP3 causes calcium release, DAG activates Protein Kinase C which phosphorylates other proteins
beta/gamma heteromer binds ion channels and modifies function
what intracellular effects does the binding of glutamate on type II and type III mReceptors have
activates g protein G alpha(i) which inhibits production of cAMP
modifies ion channels
what are the effects of glutamate binding on presynaptic metabotropic channels
causes beta/gamma heteromer to block voltage gated calcium channels - leads to less excitability
what are the effects of glutamate binding on postsynaptic metabotropic receptors
usually opens K+ channels leading to hyperpolarisation and less excitability
what is the precursor and enzyme needed for GABA synthesis
glutamate and glutamic acid decarboxylase
GABA is broken down by what enzyme
GABA transaminase
how is GABA packed into vesicles
H+ ions move out of the vesicle and simultaneously GABA moves in
how is GABA removed from synaptic cleft
1) taken up into astrocytes through a co-transporter protein which brings Na and GABA into cell (degraded by GABA transaminase)
2) into postsynaptic neurons (degraded by GABA transaminase)
3) taken up into presynaptic neurons and recycled
what kind of receptors does GABA act on
postsynpatic ionotropic
pre/postsynaptic metabotropic