GABA receptors

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

false - second most abundant (glutamate receptors are the most abundant)

what are the 2 main classes of GABA receptors

• ionotropic (ligand-gated ion channels that cause opening for ion to pass through)

• metabotropic (GPCR that work more slowly and trigger intracellular cascades)

how do ionotropic GABA receptors work

binding of GABA causes opening of channel pore to allow influx of Cl- and effluc of HCO3-

what types of GABA receptors are present within ionotropic GABA receptors

• GABA_A receptors

• GABA_C receptors

what do GABA_A receptors do

control most of synaptic transmission at GABAergic synapses in brain

what do GABA_C receptors do

expressed mainly in the retina so is ivolbed with retinal signalling process

what effect do GABAₐ receptor agonists and allosteric modulators have in epilepsy models

suppress epileptic seizures

what effect do GABAₐ receptor antagonists have in

they can induce epileptic seizures

what does this suggest about the role of GABAₐ receptors in the brain

Enhancing GABAₐ activity reduces neuronal overexcitation, while blocking it increases seizure risk

what does the binding of GABA to metabotropic GABA receptors do

binding of GABA activates heterotrimeric G proteeins and intracellular signalling pathways which regulate activity of various voltage-gated ion channels

what are GABA_B receptors

metabotropic GABA receptors

true or false: most GABA receptors are expressed presynaptically

false - expressed mainly postsynaptically

where are GABAₐ receptors found

expressed in all neurons in brain

main role of GABAₐ receptors

• normal brain function

• anxiety

• epilepsy 

• panic disorders

• insomnia

which drugs target GABAₐ receptors

• benzodiazepines

• barbiturates

• anaesthetics

• alcohol

what other substances modulate GABAₐ receptors

• stress hormones 

• neurosteroids

what type of structure do GABAₐ receptors and GABA_c receptors

pentamers (made of 5 subunits)

how many genes encode GABAₐ receptors and what are their groups

16 genes grouped into α, β, γ, δ, ε, θ, π subunits

how are GABAₐ receptors assembled

in the endoplasmic reticulum, typically from 2 α subunits, two β subunits, and one γ, δ, ε, π or θ subunit

what are GABA_c receptors composed of

formed from ρ (rho) 1–3 subunits

what determines functional properties of GABAₐ receptors

• GABA affinity

• channel properties

• drug selectivity

• expression patterns

• subcellular localisation

what type of inhibition do do GABA_ʙ receptors mediate

slow inhibitory response via G-protein coupled mechanisms

how do GABAʙ receptors work

• activate Gi/o proteins → inhibits adenylyl cyclase → reduces cAMP and PKA → opens K+ channels (hyperpolarisation) → closes Ca2+ channels (reduces neurotransmitter release)

what is a specific agonist of GABAʙ receptors

baclofen

what is the structure of GABAʙ receptors

dimers of GABAʙ1 and GABAʙ2 subunits

• GABA binds to GABAʙ1 (on extracellular domain)

• G-proteins bind to GABAʙ2 (on intracellular domain)

where are GABAʙ receptors located

• postsynaptic membrane - produce slow IPSPs

• presynaptic GABA terminals - act as autoreceptors (inhibit GABA release)

• presynaptic glutamate terminals - act as heteroreceptors (inhibit glutamate release)

what is the main inhibitory neurotransmitter in the spinal cord and brainstem

glycine

what are glycine receptors

ligand-gated chloride channels that are hetero-pentamers of α and β subunits

how many isoforms exist for glycine receptors

4 α isoforms and 1 β isoform

what happens when glycine receptors are activated in mature neurones

Cl- ions enter cell causing hyperpolarisation in postsynaptic neurone and reduced neuronal firing

what blocks glycine receptors and what are the effects

strychnine - competitive antagonist

causes over-excitation, pain, muscle cramps and exaggerated startle responses

apart from the spinal cord and brainstem, where else does glycine act as an inhibitory neurotransmitter

in the retina via glycinergic amacrine cells