Glutamate Flashcards
TRUE or FALSE: non-essential amino acids are not required in diet
TRUE
Where are non-essential amino acids synthesized?
most cells of the body
What are the 2 functional groups of the amino acid NTs?
- excitatory AA NT: glutamate, aspartate
- inhibitory AA NT: GABA, glycine
TRUE or FALSE: aspartate is released in a Na+ dependent manner
FALSE: Ca2+ dependent manner
TRUE or FALSE: Aspartate is stored in vesicles
False: just in the cytoplasm, not in vesicles
Which receptors does aspartate act on?
glutamate receptors
What is the most widely used excitatory NT?
glutamate
What percentage of neruons and synapses are glutamatergic?
- 90% of neurons
- 80-90% of synapses
What does glutatmate mediate?
fast excitatory neurotransmission (sensory, motor, emotion, cognition, memory)
Where is glutatmate most concentrated in the neuron?
presynaptic compartments
Describe the synthesis of glutamate (i.e. what enzyme)
glutamine converted to glutamate by glutaminase
How many families are there of VGLUT?
3
Glutamate is packaged into ______ to maintain a separate pool of NT.
vesicles
What can be used to identigy glutamatergic neurons?
vesicular glutamate transporter (VGLUT)
TRUE or FALSE: VGLUT is structurally and functionally similar to VMAT
TRUE
What is glutamate metabolized by? What is the end product?
glutamate converted to glutamine by glutamine synthetase
What are responsible for reuptake of glutamate?
excitatory AA transporters (EAATs)
TRUE or FALSE: EAATs are specific for glutamate
FALSE: non-specific fro glutamate and aspartate
How many families of EAATs are there?
5
Neurons comprise only _____% of the cells in the CNS. The reminains cells are termed ________.
50; glia
What are astrocytes?
define the brain side of the BBB
What are oligodendrocytes?
myelinate axons in white matterW
What are ependymal cells?
generate and regulate CSF
What are microglia?
immune surveillance and development
What do astrocytes regulate?
- intake of nutrients and O2 and blood flow in the brain
- synaptic functions and plasticity
What kind of synapses are astrocytes coupled by?
electrical synapses - gap junctions
TRUE or FALSE: human astrocytes are very dfiferent from rodents
TRUE
Grafting human astrocytes into mouse cortex ________ cognitive measures.
increases
Where are VGLUT1 and 2 expressed?
distinct glutamatergic populations in the CNS
Where is VGLUT3 expressed?
GABAergic, cholinergic, and monoaminergic neurons (modulatory function)
TRUE or FALSE: high levels of extracellular glutamate are toxic to neurons
TRUE
What does genetic KO of EAAT 1 and 2 result in?
increases in glutamate, esp in the striatum
What does KO of EAAT3 result in?
more limited effects in comparison to EAAT1 and 2
Which EAAT(s) is/are associated with astrocytes vs neurons?
- EAAT1 and 2 = astrocytic
- EAAT 3 = neuronal
Which pathway of glutamate recycling is the dominant pathway? (neuron or astrocyte?)
astrocyte
Abnormality of which EAAT is observed in ALS?
EAAT2
glutamatergic synapses are wrapped by __________ ___________ expressing ______________ and ___________.
astrocyte processes; EAAT1, EAAT2
TRUE or FALSE: glutamate uptake into astrocytes is slow and inefficient.
FALSE: rapid and high efficiency
What is the principal site of glutamate breakdown?
astrocyte
Describe the recycling of glutamate in the synapse?
glutamine is exported from astrocytes and taken up into neurons to be converted back to glutamate
What kind of synapse is there for glutamate?
tripartite synapse
What substance can be used experimentally to induce glutamatergic lesions?
MSG
TRUE or FALSE: MSG is proposed as one of the 5 basic tastes (salty)
FALSE: umami
MSG acts on glutamate receptors on the _______.
tongue
Is MSG syndrome real?
no
Where are EAAT1 and 2 expressed?
astrocytes
Where are EAAT3 and 4 expressed?
neurons
Where are EAAT5 expressed?
retina
What kind of neurons of the cerebral cortex are involved in glutatmatergic signaling?
pyramidal neurons
Which tracts are glutamatergic?
corticospinal tract (voluntary motor control)
Which fibers of the cerebellum are glutamatergic?
parallel fibers (excitatoary inputs to Purkinje cells)
Which brain structure inovlved in memory is highly associated with glutamatergic signalling?
hippocampus
What are the glutamatergic ionotropic receptors?
AMPA, kainate, NMDA
TRUE or FALSE: glutamate is repsonsible for FAST excitiatory synaptic transmission
TRUE
TRUE or FALSE: AMPA receptors are selective for Na+
FALSE: non-selective cation channel (Na+ and K+)
How many subunits of AMPA receptors are there? What do they form?
- 4 types (GluR1-4)
- heterotetramers (dimers of dimers)
TRUE or FALSE: AMPA receptors have slow kinetics
FALSE: rapid
What results from a mutation in AMPAR GRIN2A gene?
58% decrease in Parkinson’s risk, if also a heavy coffee drinker
Which receptor are kainate receptors functionally similar to?
AMPA receptors
How many subunits of kainate receptors are there?
5 subunits
What is the selective agonist of kainate receptors? Where is it isolated from?
kainate, isolated from red seaweek
TRUE or FLASE: kainate receptors are faster than AMPAR
FALSE: slower than AMPAR
Where can kainate receptors be expressed presynaptically?
GABAergic synapses
TRUE or FALSE: kainate receptors hav e a limited role in fast, excitatory transmission
TRUE
Which two excitatory receptors are difficult to distinguish experimentally?
kainate and AMPA receptors
What do agonists at kainate and AMPA receptors cause?
seizures
What is used as a model of epilepsy?
kainic acid
How can you experiemtnally induce spontaneous seizures?
repeated administration of kainic acid
What are the agonists of AMPA and Kainate? Describe the selectivity.
- kainate/kainic acid - kainate receptor
- AMPA - AMPAR
- domoic acid - kainate receptor
What does domoic acid cause in humans?
amnesiac shellfish poisoning
What are the antagonists of kainate and AMPA receptors? What is the selectivity?
- NBQX - AMPAR
- NS102 - kainate receptor
TRUE or FALSE: glutamatergic synaptic transmission eleicits excitatory postysnaptic potentials (EPSP)
TRUE
What ions are NMDA receptors permeable to?
Na+, K+, Ca2+
What ions are AMPARs permeable to?
Na+ and K+
Where are NMDA receptors found?
widely distributed: cortex, huppocampus, basal ganglia, septum, cerebellum
What are NMDARs always co-expressed with?
either AMPA or kainate receptors
How many binding sites are there for NMDARs
6 - highly regulated
NMDARs are important in ________ and ________ processes by modulating ______ ______.
learning and memory; synaptic strength
What are the obligatory agonist binding sites of NMDAR?
glutamate and glycine/D-serine sites
Describe NMDAR gating
- Mg2+ occupies NMDAR channel pore
- agonist binding alone cannot open the channel
- previously present depolarization displaces Mg2+ (voltage-dependent)
- NMDAR only active after initial depolarization (through AMPAR)
What are the endogenous agonists of NMDAR?
- glutamate and glycine/D-serine (obligatory)
- polyamines - allosteric modulators
What are the exogenous agonists of NMDAR?
NMDA - synthetic AA
What are the endogenous antagonists of NMDAR?
Zn2+ (allosteric), Mg2+
What are the exogenous antagonists of NMDAR?
MK801, PCP, ketamine
What is MK801 used for? Is it competitive or non-competitive?
- widely used experimental antagonist of NMDAR
- non-competitive
What is the function of PCP and ketamine? Are they competitive or non-competitive?
- dissociative anesthetics/recreational
- non-competitive
What is the significance of the polyamine binding site of NMDAR?
site of endogenous allosteric modulation (positive)
What is the significance of the Mg2+, Zn2+, and H+ binding sites?
- Mg2+ - voltage-dependent bloc of channel opening
- Zn2+ - negative allosteric modulation site
- H+ - pH sensitive egative modulation
Why is NMDA described as a coincidence detector?
opens only under conditions of strong or repeated stimulation