Amine transporters - part 1

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What determines neuronal output
An integrated response of the strength of induvidual inputs and whether they are excitatory of inhibitory
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Example of a major excitatory transmitter
Glutamate
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Example of major inhibitory transmitters
GABA and Glycine
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Where is glutamate sunthesised? Why?
In the brain - it doesn't cross the blood brain barrier.
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How is it synthesised? Two ways
from metabolism of glucose, or from glutamine synthesised by astrocytes.
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How is it synthesised from glutamine?
By the enzyme Glutaminase. Glutamine synthase works in the other direct
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How is glutamate removed from the synapse
Uptake by transporters
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How does glutamate accumulate in synaptic vesicles
VGluT1-3, driven in by an eectrical gradient created by different concentrations of H+.
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How is this electrical potential gradient generated?
ATP proton pump.
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What is the vesicle concentration, how many molecules per vesicle
>20mM, 1000-2000 molecules per vesicle.
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What transporters reuptake glutamate
Excitatory Amino Acid Transporters - EAATs
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How do glutamate transporters drive uptake
Co-transport of Na+ and H+ into the cell, and counter transport of K+
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Where are most transporters located
Glial cells, with some on post synaptic neurons.
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The two large families of glutamate receptors
ionotropic and metabotropic
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The three classes of ionotropic glutamate receptors
NMDA, AMPA, Kainate.
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What do metabotropic glutamate receptors do
Have a moldulatory effect on neuronal fucntion and synaptic transmission
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Antagonist for the AMPA receptor
CNQX
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Antagonist for the NMDA receptor
Phencyclidine, Ketamine, MK-801,
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Kainate antagonists
CNQX, LY294486
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Where are AMPA and NMDA receptors located in the brain?
they often co-localise at functional excitatory synapses, NMDA are widespread. Small number of Kainaite receptors
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The subunits of ionotropic glutamate receptors.
each one has three transmembrane spanning domains with a large extracellular N terminus. The receptors are all made up of 4 subunits.
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The AMPA receptor
Assembled from GluA1-4, 2 of one type and then 2 of another. They are all permeable to Na+ and K+, and some are Ca2+ permeable.
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NMDA receptors
2 GluN1 and 2GluN2 subunits. They are permeable to Na+, K+ and Ca2+
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Kainate receptors
GluK1-3 can form functional homomeric or heteromeric channels, GluK4 or 5 need combine with one of GluK1-3. Permable to Na+
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How does the AMPA receptor contribute to the EPSP
Fast synaptic current and fast decay, because of low affinity
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How does the NMDA receptor contribute to the EPSP
Slower onset and slower decay, due to higer affinity glutamate binding
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How are NMDA receptors voltage sensitive
at membrane potentials
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How do NMDA receptors act as co-incidence detectors
Needs repetative or multiple excitatory inputs from other AMPA receptors to depolarise the neuron and releive the Mg2+ block
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What do NMDA recetprs require to function?
Glutamate binding to the GluN2 subunit, glysince binding to a site on the Glun1. Drugs that prevent glycine binding will inhibit NMDA receptors
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How many metabotropuc glutamate receptors are there
8 known ones - mGlur1-8
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How many groups and what are they grouped according to
amino acid sequence homology, agonist pharmacology and signal transduction pathways. Groups I II and III
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Which ones are in group 1
MGlur1, mGlur5
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What do the ones in group 1 do
Activate phospholipase C, leading to increase intracellular Ca2+, and protien phosphorylation via PKC.
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What ones are in group 2
mGlur2 and mGlur3
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which ones are in group 3
mGluR4, mGlur6-8
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What do group 2 and 3 ones do?
Inhibit adenylate cyclase and decrease cAMP levels, modify ion channel activity
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What are the presynaptic effects of all mGlurs
inhibition of voltage gated ca channels, to reduce transmitter release from other terminals.
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What are the post synaptic effects of mGlurs - mostly group 1.
Inhibit K+ channels to increase excitability. Increase the activity of some K+ channels. Depends on what cell
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What is the full name of GABA
Gamma amino butyric acid
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How is it formed?
From glutamate by action of the enzyme Glutamic acid decarboxylase.
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How is it destroyed
GABA transaminase within cells, which turns it into succinic semialdehyde
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How is GABA packed in vesicles
in the same way as glutamate - H+ gradient potential
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How is GABA removed from the synapse
Energy from Na is used to drive reuptake through cotransport. It is reutilized in pre-synaptic neurons and broken down in glia?
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Define what type GABAa and GABAb receptors are
GABAa = ionotropic post. Gabab = metabotropic, pre and post
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Composition of the GABAa receptor
5 subunits, 2a, 2b and 1y. Each subunit has 4 transmembrane domains. 2 binding sites
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What ions can go through?
Cl- selective, mediate fast inhibition
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Other cards in this set

Card 2

Front

Example of a major excitatory transmitter

Back

Glutamate

Card 3

Front

Example of major inhibitory transmitters

Back

Preview of the front of card 3

Card 4

Front

Where is glutamate sunthesised? Why?

Back

Preview of the front of card 4

Card 5

Front

How is it synthesised? Two ways

Back

Preview of the front of card 5
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