Neuroscience - Neurotransmitter receptors Flashcards
What are the 2 main classes of neurotransmitter receptors?
- Ionotropic receptors
- G-protein coupled (metabotropic) receptors
What does transmitter binding cause in both ionotropic and G-protein coupled receptors?
Ionotropic - binding opens an ion channel
G-protein coupled - binding activates a G-protein which, in turn, activates an effector e.g. enzyme, ion channel
What are the 2 main types of ionotropic receptors?
- cys-loop receptors
- p-loop receptors
Cys-loop receptors are the receptors for what transmitters?
- Nicotinic ACH
- GABAa
- Glycine
- Serotonin 5-HT3 subclass
P-loop receptors are the receptors for what transmitter?
Glutamate (iGluR)
What are the main 2 types of G-protein coupled receptor?
Class A and C
Class A receptors are the receptors for what transmitters?
Muscarinic ACH Dopamine Serotonin 5-HT1-2,4-7 subclasses alpha and beta adrenergic Most neuropeptides
Class C receptors are the receptors for what transmitters?
Glutamate (mGluR)
GABAb
How was nACHR first isolated?
Isolated from the electric organ of electric fish
- dense arrays of nACHRs
What is the subunit organisation of the nACHR?
- Individual subunits designated alpha, beta, gamma, delta and epsilon
- Each individual subunit has 4 transmembrane (TM) domains and extracellular N- and C- termini
- 5 subunits assemble a pentameric structure
- TM2 from each subunit lines the pore of the ion channel
- 2 alpha subunits, which bind ligand, are required for a functional receptor
How many individual subunits are there in total? How many of each? (e.g how many alpha, beta etc)
17 subunits in total 10 alpha 4 beta 1 gamma 1 delta 1 e
Different combinations of subunits cause what?
Different pentameric receptors with different conductance properties
Give an example of how different subunits can cause different conductance?
Receptors composed of alpha and beta subunits more permeable to Ca2+
What structural feature of the nACHR facilitates cation permeability?
The pore is surrounded by rings of negatively-charged amino acids
Per receptor, there are always 2 subunits of what type?
alpha
Where does the ligand bind to on the nACHR?
- Binds to the N-terminal extracellular domain of alpha subunit and adjacent adjacent subunit (varies depending on receptor type)
What is the positive and negative face of the nACHR and what does each determine?
Positive - alpha-subunit side - determines ligand affinity
Negative - adjacent subunit - determines ligand selectivity
What distinguishes the alpha subunit from a non-alpha subunit?
2 neighbouring cysteine residues distinguish alpha from non-alpha subunits
What amino acids are important for binding on the negative face?
Leucine, methionine and tryptophan
What facilitates nACHR channel opening/closing
- Rotation of TM2 domains of each of the 5 receptor subunits closes or opens a ring of leucine and valine residues to regulate ion movement
What amino acids line the channel to facilitate ion permeability?
Serine and threonine
What are the 3 groups of ionotropic glutamate receptors (iGluR)?
1) NMDA
2) AMPA
3) Kainate
What family of ionotropic receptors are iGluRs part of?
pore-loop channels
(p-loop channels)
includes the voltage gated K+ and Na+ ion channels
What is the subunit organisation of the iGluR?
- Each subunit has 3 TM domains and one re-entrant hairpin loop
- Hairpin loop forms the pore of the receptor chennel
- Extracellular domains including N-terminus and TM2-TM3 loop are very large
- C-terminus is intracellular
- Receptor is a tetramer of 4 subunits
