glutamate receptors

true or false: glutamate receptors are the most abundant neurotransmitter receptors in the brain

true

other types of neurotransmitters in the brain that lead to EXCITATORY effects (and therefore cause depolarisation)

• acetylcholine

• catecholamine (noradrenaline, dopamine)

• serotonin

• GABA

what receptor(s) does acetylcholine activate

• ionotropic nicotinic receptors → depolarisation

• metabotropic muscarinic receptors

difference between ionotropic and metabotropic receptors

• ionotropic - fast-acting ligand-gated ion channels that open immediately when a neurotransmitter binds, causing rapid ion flow and changes in membrane potential

• metabotropic - indirect, slower, G-protein coupled receptors (GPCRs) that trigger long-lasting intracellular cascades, leading to more prolonged effects

how does acetylcholine binding to metabotropic muscarinic receptor lead to depolarisation

because voltage gated K+ channels are inhibited

what receptor does serotonin activate

ionotropic 5HT3 receptors

why can dopamine and noradrenaline have both excitatory and inhibitory effects

because it depends on their intracellular signalling pathway

how can nitric oxide (NO) lead to excitatory effects

activates presynaptic cGMP signalling

what are glutamate receptors classified as

• ionotropic glutamate receptors ae ligand-gated ion channels which means binding of glutamate causes opening of channel pore to allow ion influx

• whereas metabotropic glutamate receptors are GPCR where binding of glutamate actives G-proteins and intracellular signalling pathways

what can ionotropic glutamate receptors be further classified as

• AMPA

• NMDA

• kainate receptors

how are AMPA, NMDA, kainate receptors distinguished

because they show different cation permeability and sensitivity to agonist and antagonist

true or false: NMDA receptors and soma AMPA receptors mediate influx of Ca2+ which causes further depolarization

true

true or false: AMPA and NMDA are mainly presynaptic receptors whilst kainate are only postsynpatic

false: AMPA and NMDA receptors are predominantly postsynaptic receptors while KAINATE receptors are both postsynaptic and presynaptic receptors

where are kainate receptors found (post/pre)

presynaptic and postsynaptic

AMPA receptors

next round of flashcards based on AMPA only

what is AMPA receptors responsible for

fast excitatory synaptic transmission in CNS

what are AMPA receptors formed as

formed as tetramers of subunits GluA1-4 which are encoded by separate gene

each subunit has large extracellular N-terminus and large intracellular C-terminus and 4 TM domains

how many sites does AMPA receptors have where glutamate can bind

4 sites

role of N-terminal domain

site formed for glutamate to bind is made of N-terminal and extracellular loop

role of C-terminal

intracellular trafficking and synaptic clusturing

how can AMPA should rapid densensitisation

because these receptors open and close very quickly

characteristic difference between AMPA made of GluA1,3,4 subunits vs GluA2 subunit

• GluA1,3,4 subunits which have higher permeability to Ca2+ than AMPA receptors which contain GluA2 subunit

this is because of RNA editing of GluA2 subunit mRNA

what does drug topiramate do

anti-epileptic drug that inhibits AMPA receptors

NMDA receptors

next few flashcards based on NMDA receptors only

how are NMDA formed 

formed as tetramers composed of two GluN1 subunits, and two GluN2A, GluN2B, GluN2C or GluN2D subunits

• all submit are products of separate genes

true or false: each subunit has a large extracellular N-terminus and a large intracellular C terminus and four transmembrane domains

true

what is required for activation of NMDA receptors

binding of both glutamate and co-agonist glycine

why is binding of both glutamate and co-agonist glycine required for activation of NMDA

because their binding is allosterically coupled

• recognition site for glycine is found on the GluN1 subunit

• site for glutamate is located on the GluN2 subunit

what is the voltage-dependent block

NMDA receptors are blocked by Mg2+ at resting potential

which ions are NMDA selective for

Na+, K+ and Ca2+

true or false: changes in NMDA channel function are associated with initiation and spread of seizures in epileptic patients

true

what is drug felbamate

anti-epileptic drug which blocks NMDA receptors

how does a larger EPSP form

AMPA receptors usually co-exist at the same synapse with NMDA receptors and they synergise in their excitatory activity. This means that activation of AMPA receptors occurs initially leading to a small EPSP, which then activates NMDA receptors by removing the Mg2+ ions from the NMDA channel

kainate receptors

next few flashcards are on kainate receptors

what agonist selectively activates kainate receptors

kainate (kainic acid)

how are kainate receptors distinct from other glutamate receptors

are a separate receptor type that is selectively activated by kainate

what subunits make up kainate receptors

GluK1–3 and GluK4–5 subunits

what kind of assemblies can GluK1–3 subunits form

functional heteromeric and homomeric assemblies

what is the glutamate affinity of receptors made only from GluK1–3 subunits

they have low affinity for glutamate

what happens when GluK1–3 subunits assemble with GluK5 subunits

they show full receptor activity

dscribe the structure of a kainate receptor subunit

each subunit has a large extracellular N-terminus, a large intracellular C-terminus, and four transmembrane domains.

what ions are kainate receptor channels permeable to

Na⁺, K⁺, and some subtypes to Ca²⁺

where can kainate receptors exert their actions

both pre and postsynaptically

how is the distribution of kainate receptors in the brain described

limited distribution

metabotropic glutamate receptors

where are metabotropic glutamate receptors found

widely expressed in the brain

how do metabotropic receptors transmit signals

through G-protein signalling and indirectly modulate function of enzymes and channels involved in excitation

true or false: in the intracellular domain, metabotropic receptors have the binding site for glutamate

false - in the extracellular domain (outside the cell)

true or false: metabotropic glutamate receptors are responsible for a fast transmission

false - slow transmission (seconds to minutes) because of the GPCR mechanism which involves many steps

what are the three groups of metabotropic glutamate receptors (mGluRs)

• group I ((mGlu1, mGlu5)

• group II (mGlu2, mGlu3)

• group III (mGlu4, mGlu6, mGlu7, mGlu8)

there are 3 main groups of metabotropic receptors, which group(s) lead to excitatory and inhibitory response

which receptors belong to group I

mGlu1 and mGlu5

what type of G-protein do Group I mGluRs activate

heterotrimeric Gq/11 proteins

what enzyme do Group I mGluRs regulate

phospholipase C (PLC)

what secondary messengers are produced by Group I mGluR activation

diacylglycerol (DAG) and inositol triphosphate (IP₃)

how do Group I mGluRs affect intracellular calcium

they increase intracellular calcium signaling

are Group I mGluRs excitatory or inhibitory

excitatory - they increase neuronal activity

which receptors belong to Group II mGluRs

mGlu2 and mGlu3

what type of G-protein do Group II mGluRs activate

heterotrimeric Gi/o proteins

what enzyme’s activity is inhibited by Group II mGluRs

adenylyl cyclase

what second messenger is decreased by Group II mGluR activation

cAMP

are Group II mGluRs excitatory or inhibitory

inhibitory - they reduce neuronal activity

which receptors belong to Group III mGluRs

mGlu4, mGlu6, mGlu7, and mGlu8

what type of G-protein do Group III mGluRs activate

heterotrimeric Gi/o proteins

what effect do Group III mGluRs have on adenylyl cyclase and cAMP

they inhibit adenylyl cyclase and decrease cAMP production

are Group III mGluRs excitatory or inhibitory

inhibitory - reduce neuronal activity

what happens when mGluRs are localized presynaptically

they act as presynaptic autoreceptors

what is the effect of presynaptic mGluR activation

inhibition of glutamate release

summary of signalling cascade for group I (excitatory)

summary of signalling cascade for group II and group III (inhibitory)