Receptors and Subunits Flashcards
How many subunits make up an AMPA receptor?
4
What are the different types of AMPA receptor subunits?
GluA1, GluA2, GluA3, GluA4
Which subunit of AMPAR determines low calcium permeability? Why is this?
GluA2 (which most AMPAR have) - because positive arginine is expressed instead of neutral glutamine.
Is AMPAR inotropic or metabotropic?
It is an ionotropic non-selective cation channel (so sodium ions in, potassium ions out)
What type of receptors are Kainate receptors?
Ionotropic
How many subunits for Kainate receptors have?
4
What are the possible subunits in a Kainate receptor?
GluK1, GluK2, GluK3, GluK4 and GluK5
Which Kainate receptor subunits do not form functional receptors when expressed alone?
GluK4 and GluK5
What does the Q/R site in Kainate receptors determine?
GluK1 and GluK2’s permeability for calcium ions.
Which subunit is necessary for Kainate receptors to make an excitatory postsynaptic response?
GluK2
What are the names of NMDA receptor subunits?
GluN1, GluN2A, GluN2B, GluN2C, GluN2D, GluN3A and GluN3B
NMDA receptors are heterotetramers of what?
Two GluN1 (NR1) subunits and two GluN2 (NR2) subunits
Which section of the NMDA receptor is the glycine binding site in?
NR1
Which section of the NMDA receptor is the glutamate binding site in?
NR2
Which receptor has the ‘Mg2+ block’?
NMDA receptors
What type of receptors are NMDA receptors?
Ionotropic
Which metabotropic glutamate receptors are part of Group 1, what type of GPCR are they and how do they signal?
mGlu1 and mGlu5
Galphaq signalling leading to increased phospholipase C, increased IP3 and increased calcium ion concentration.
Which metabotropic glutamate receptors are part of Group 2, what type of GPCR are they and how do they signal?
mGlu2 and mGlu3
Galphai/o, leading to decrease in activation of andenylyl cyclase and consequently cAMP and decreased calcium ion concentration.
Which metabotropic glutamate receptors are part of Group 3, what type of GPCR are they and how do they signal?
mGlu4, mGlu6, mGlu7 and mGlu8
Galphai/o leading to decrease in activation of andenylyl cyclase and consequently cAMP and decreased calcium ion concentration.
Which postsynaptic metabotropic glutamate receptors mediate slow depolarisation?
mGlu1 and mGlu5 (aka Group 1)
Which groups of presynaptic metabotropic glutamate receptors decrease neurotransmitter release?
Group 2 and Group 3
What type of receptors are Glycine receptors?
Ionotropic
How many subunits are Glycine receptors comprised of?
5
What type of receptors are GABA-A receptors?
Ionotropic
What is the most common combination of subunits of GABA-A receptors in the mammalian brain?
1 x alpha, 2 x beta and 2 x gamma
How many subunits create a GABA-A receptor?
5
Benzodiazepines do not work on GABA-A receptors containing which subunits?
Alpha 4 and/or alpha 6
What are names of the possible GABA A subunits?
Alpha1-6, Beta1-3, Gamma1-3, Delta, Epsilon, Pi, Theta and Rho1-3
What subunits are most GABA A receptors comprised of?
2 Alpha, 2 Beta and 1 Gamma/1 Delta
Where do benzodiazepines bind to on the GABA A receptor?
The alpha gamma subunit interface
What type of receptors are GABA B receptors?
GPCR/Metabotropic
What type of GPCR is a GABA B receptor? What are the downstream effects of binding?
Galphai/o - they are negatively couple to adenlyl cyclase leading to inhibition of cAMP production, activated GIRK potassium channels and inhibits voltage sensitive calcium channels.
What is the molecular target of the Group 1 anaesthetics (e.g. Etomidate, Propofol and Pentobarbitol)?
GABA A Receptor
The presence of which GABA A receptor subunit abolishes potentiation of the IV anaesthetic Etomidate?
Beta3
A mutation in which GABA A receptor subunit reduces the hypnotic response and abolishes the immobility response to Etomidate and Propofol?
Beta3
Group 2 anaesthetics (e.g. Nitrous Oxide, ketamine, xenon and cyclopropane) act on which molecular targets?
NMDA receptors, AMPA receptors, neuronal ACh receptosrs and 2 pore potassium channels.
Group 3 anaesthetics (the halogenated ethers and alkanes, such as isofluorane and halothane) act on which molecular targets?
GABA A receptors, glycine receptors, NMDA receptors, AMPA receptors, neuronal ACh receptors and 2 pore potassium channels.
Anaesthetic potency of propofol correlates with its ability to…?
Potentiate GABA A receptor mediated chloride currents.
Hypnosis and amnesia in anaesthesia is due to potentiation of which receptor?
GABA A receptor
Immobilisation in anaesthesia is mediated by potentiation of which receptor?
Glycine receptor
Inhibition of which receptor leads to analgesia during anaesthesia?
NMDA receptors
What two receptors have other unspecified contribution to anaesthetic effects?
Neuronal ACh receptors and potassium channels.
Which receptor is in both the sympathetic and parasympathetic autonomic nervous systems?
Nicotinic cholinergic receptors
Which type of receptor is only present in the sympathetic section of the autonomic nervous system?
Adrenergic receptors
Which type of receptor is only present in the parasympathetic section of the autonomic nervous system?
Muscarinic receptors
What are the different isoforms of muscarinic receptors in the parasympathetic nervous system and how do they signal?
M1, M3 and M5 - stimulate phospholipase C
M2 and M4 - inhibit adenlyl cyclase
What are the different isoforms of adrenergic receptors in the sympathetic nervous system and how do they signal?
Alpha1 - activates phospholipase C
Alpha2 - Inhibits adenlyl cyclase
Beta1, Beta,2 and Beta3 - Increase cAMP
What are the different types of dopamine receptor and how do they signal?
D1-like (D1 and D5) - GalphaS - increases cAMP
D2-like (D2, D3 and D4) - Galphai - decreases cAMP
Which dopamine receptor can be an autoreceptor?
D2
Which 5-HT receptor’s a Galphai/o leading to decreased cAMP?
5HT1A, 5HT1B, 5HT1D, 5HT1E and 5HT1F
Which 5HT receptor is a ligand gated ion channel?
5HT3
Which 5HT receptor is GalphaS that is implicated in learning and memory?
5HT6
Which 5HT receptor is implicated in modulation of exploratory behaviour? What type of GPCR is it?
5HT5A - GalphaS
5HT4 is which type of GPCR?
GalphaS
Which serotonin receptor is an inhibitory presynaptic receptor that becomes desensitised after chronic SSRI treatment?
5HT1A receptor
Which serotonin receptors are Galphaq, therefore leading to increased DAG and IP3?
5HT2A, 5HT2B and 5HT2c
LSD is mainly an agonist of which receptor?
5HT2A receptor
Psilobycin is an agonist of 5HT2AR but also has high affinity for which receptors?
5HT2B and 5HT2C
Which agonism of which serotonin receptor is necessary for the effects of ‘classic’ hallucinogens?
5HT2A receptors
Which receptor does cortisol behind to?
Glucocorticoid receptors
What does activation of glucocorticoid receptors lead to in glutamatergic synapses?
Induces glutamate release, endocannabinoid production and can exacerbate glutamate induced excitotoxicity.
Which cannabinoid receptor is expressed in the brain, lungs and liver?
CB1 receptor
What type of GPCR is CB1? What effect does it have?
Galphai/o - positively regulates GIRK channels, negatively regulates calcium channels and inhibits adenlyl cyclase leading to decreased cAMP
Is CB1 pre or postsynaptic?
Presynaptic
What type of GPCR are all opioid receptors?
Galphai/o
How do opioids suppress pain?
Act as presynaptic receptor e.g. mu opioid receptor suppresses calcium channel opening, reducing synaptic transmission and therefore reducing transmission of pain signals up to sensory cortex.
What type of GPCR is A1 Receptor?
Galphai/o - decreases cAMP
What type of GPCR is A2A receptor?
GalphaS - increasing cAMP leading to increased GABA release
