Ionotropic/metabotropic Receptors Flashcards
Inward current produces a _____ deflection?
Downward
Current is a measure of ion flow in what direction?
Direction of POSTITIVE ion
Opposite direction to -ve ion
Membrane potential (EPSP/IPSP) is a __________ of the current (EPSC)?
Mirror image
IONOTROPIC receptors consist of how many subunits?
4 or 5
Which subunits of the nAChR have the ACh binding sites?
2 alpha subunits
The transmembrane domains of each subunit are arranged so that which domain forms the pore?
TM2
Each TM2 has what that forms the selectivity filter?
This makes nAChR selective to____?
Negatively charged AAs
cations
How do muscle and brain nAChRs differ?
1) SUBUNITS: - muscle has 2a, B, d, y or E.
- brain 3a, 2B or 5a
2) Muscle nAChR binds alpha BUNGAROTOXIN, brain does not
Other than nACh what other IONOTROPIC receptors are there (7)?
AMPA, NMDA, kainate, 5-HT, purines, GABA, glycine
What are the 3 types of IONOTROPIC glutamate receptors and their possible subuints?
NMDA (NMDAR1, NMDAR2a-d, NMDAR3a-b)
AMPA (GluR1-4)
Kainate (GluR5-7, KA1, KA2)
How many subunits do ionotropic glutamate receptors have?
4
Tetramers
What is the major receptor for excitatory transmission?
AMPA
What is the structure of an AMPA receptor?
What are the two most common conformations?
Dimer or dimers
GluR1/GluR2: -most common, allows Na+ to pass. GluR2 controls Ca permeability, prevents Ca entry
GluR1/GluR1: - formed due to activity/insult. Allows passage of Na and Ca => larger depolarization (+ Ca acts as 2nd messenger)
What stimulates an increase in expression of AMPA receptors (esp GluR1 hetromer) in postsynaptic membrane?
Lots of synaptic activity
What is the subunit composition of an NMDA receptor?
2 x NR1 (glycine) 2x NR2 (glutamate)
What is the role of glycine in NMDA receptor?
Co-agonist
Need both glut and glyc to open channel
What ions does the NMDA receptor allow to pass when open?
Why is the channel not open at resting potentials?
Na, Ca (and K)
Pore blocked by Mg2+
NMDA receptor is known as a _______ detector?
Coincidence
Explain why inward current of NMDA receptor is voltage-dependent
Resting potentials- pore blocked
Upon depolarization (due to AMPA activation) Mg2+ is forced out of pore, allowing influx of Na/Ca
NMDA activity needs high-frequency stimuli
What is the Ca2+ entering NMDA (acting as 2nd messenger) important for?
Long term potentiation
important for learning and memory
The function of which receptor is important for synaptic plasticity?
NMDA
Describe the current through an AMPA and NMDA receptor?
AMPA: rapid rise in current but v transient (dissipates quickly)
NMDA: slower activation, current doesn’t reach max, but sustained/lasts longer
GABAa receptors have binding sites for _______ that change effect of GABA binding on the receptor?
Allosteric modulators
What effect do benzodiazepines have on GABAa?
Potentiate GABA activity
Agonist
Increase frequency of channel opening
What effect do barbiturates have on GABAa?
Agonist
Increase binding of GABA and benzodiazepines
Increase time channel open (increased Cl- flux)
Steroids have similar effect on GABAa as_____?
Barbiturates
What effect do picrotoxins have on GABAa?
Inhibit channel
Acts on gating process
Decreases time channel open
What allosteric modulator binding sites are located in the pore of GABAa?
Barbiturates, steroids, picrotoxin
How many subunits form GABAa?
Which subunits have GABA binding sites?
5 (pentameric)
B subunits
What is the common structure of metabotropic receptors?
What are exceptions to this?
Monomeric
Glutamate and GABA receptors = dimers
G proteins are _____ proteins?
Trimeric
Which G protein subunit binds GDP and interacts with GPCR?
Alpha
What happens upon activation of a G-protein when it interacts with GPCR?
GDP replaced by GTP
a subunit dissociates from By subunits
How do G-protons return to inactive state?
a subunit hydrolyses GTP to GDP
a re associates with By
What is special about GTP-y-s which binds G proteins?
Can’t be hydrolysed
Subunits remain active
Give 8 metabotropic receptor classes
Glutamate, GABAb, histamine, 5-HT, purines, dopamine, NA/Ad, muscarinic
How many classes/groups of mGluRs (mGluR1-7) are there?
Which receptor subtypes are in each class?
3
Group I: mGluR1 + mGluR5
Group II: mGluR2 + mGluR3
Group III: mGlurR4,6,7,8
Group I mGluRs are coupled to which type of G protein?
And located mostly pre or post synaptic?
Gq (PLC -> DAG + IP3 -> PKC + Ca -> increased protein phos + activated Ca binding proteins)
Postsynaptic
Group II mGluRs are coupled to which type of G protein?
And located mostly pre or post synaptic?
Gi (inhibits ad cyc and cAMP -> decreased pka an decreased protein phos)
Presynaptic
How are mGluRs modulatory?
Modulate neurone and determine future cell response
Make cell more or less likely to fire
How specifically are group I mGluRs modulatory ?
Gq -> PKC
PKC modulates AMPA receptors, internalises receptors so glut can’t bind
Can’t contribute to future EPSPs, less likely to be excited
What is the modulatory effect of group II mGluRs?
Gi -> inhibit cAMP
Reduce NT release
GABAb is a hetrodimer. Which monomer binds GABA?
R1
Activation of GABAb is inhibitory, how?
Coupled to Gi
Decreased protein phosphorylation
Increased k+ channel activity (hyper polarises cell)
Inhibits Ca channels (less Ca influx = less NT release)
