Neurotransmitter Receptor Signalling Flashcards
What makes an neurotransmitter an excitatory neurotransmitter
Chemical binds to post-synaptic receptors that has excitatory effects
What ionotropic receptors do glutamate bind to
iGluRs (AMPA, Kainate, NMDA receptors)
What metabotropic receptors do glutamate bind to
mGluRs (grp1,2,3)
Outline AMPA receptors subtype
Each receptor consists of 4 subunits combined together around a central pore that allows cations to pass through
-not permeable to calcium- Q/R site determines Ca2+ permeability of GluA2
What are the properties of AMPA receptors?
Mediate majority of fast excitatory synaptic transmission
GluA2 subunit causes very low Ca2+ permeability- causes an influx of Na+
Outline kainate receptor subtypes
Similar subunit topology to AMPA
GluK4+5 expressed alone in a tetramer do not form functional receptors
Outline the structure of NMDA receptors
-cation channel opening causing depolarisation
-activation requires binding of glutamate and a co-agonist - glycine or D-serine
-has a voltage sensitive Mg2+ block which is present at physiological concentrations of Mg2+ but disappears when the cell is depolarised
What does is mean by the NMDA receptor is a coincidence receptor?
-AMPARs often present at same synapse as NMDARs. Depolarisation of membrane removes Mg2+ block of NMDARs
-Only activated/Ca2+ entry when pre-synaptic cell is activated and post-synaptic cell is activated
Outline the structure of mGlu receptor
One subunit but 7 transmembrane domains
Second intracellular loop involved in G-protein coupling
Outline the properties of metabotropic glutamate receptors
Can be located pre/post-synaptically
Modulating synaptic transmission through potassium and calcium
Which metabotropic glutamate receptor is postsynaptic and which are presynaptic, and what effects do they have?
Postsynaptic- group 1- slow depolarisation
Pre-synaptic- group 2 & 3-decrease neurotransmitter release
What inhibitory receptors do GABA bind to
IGABARs (A+C) -ionotropic
GABAbRs-metabotropic
Outline the GABAa receptor structure
-5 subunits; two alpha receptors, two beta receptors and one gamma subunit
-make a chloride ion channel (anion)- channel opening causing hyperpolarisation
What do GABAa receptors do?
Mediate fast inhibitory synaptic transmission
Outline metabotropic GABAb receptors
Dimer- two G-coupled protein receptor
-GABAb1 and GABAb2 receptor present
Located pre and post-synaptically
How is neural function modulated by alcohol
-alters lipid composition
-interacts with polar heads of phospholipids
-disturbs the relationship of protein in membrane
-direct interaction with channel protein
-modifies gating mechanism inside channel
-acts as a neurotransmitter binding site
How can alcohol modulate glutamatergic Neuro transmission
-non-competitive antagonist
-reduce glutamate release from pre-synaptic terminal by increasing activity of mGluR2/3
How does ethanol inhibit NMDA mediated currents
Reversibly inhibits NMDA-induced inward currents in cultured neurons (voltage clamps)
How can alcohol modulate GABAergic Neuro transmission
-positive Allosteric modulator
-enhanced GABA release
Chronic exposure leads to reduced impact
-change in GABAa receptor subunit composition
-no pronounced change in receptor number
