GABARs: Genes, receptor subtypes and activation mechanism Flashcards
What is the main purpose of drugs that target GABARs?
Induction and maintenance of anesthesia
How many genes encode GABARs?
a LOT
What are the 2 or 3 types of GABARs?
BDZ sensitive or insensitive (GABA-rho in retinas too)
What is the quaternary structure of GABARs?
Obligate pentamer
Where are GABARs located in the brain and what is a consequence of this?
GABARs are widespread throughout the brain and thus, Benzodiazepines have a huge effect
(GABA is like a brick trying to stop a car, it depends where you stick it)
What ion does GABA shuttle? What is the net effect on the potential difference of the neuron?
Cl-
Shuttles anion into cell, hyperpolarizing it
What else can GABA regulate?
pH
Describe the heteromericity of the GABA A receptor
Always at least one or two alpha subunit and one or two beta subunit, the other 1-3 subunits are either delta or gamma (but there can be others such as rho or pi)
Where do GABARs with the delta subunit localize? The gamma subunit?
Delta: extrasynaptic site
Gamma: Synaptic site
Which subunits confer BDZ sensitivity?
Gamma and any alpha subunit that is not 4 or 6
On which sides of the cell do the N and C termini of the GABA A Receptor subunit lie?
Both termini are outside of the cell
Why is there so much redundancy in GABAR subunits? eg theres 6 alpha subunits
Different subunits have slightly different functions and different localizations
Selectively blocking one receptor type and not the other leads to different effects (with some crossover) eg anxiolysis and sedation
Describe the 3 types of ways GABA can be released
In inhibitory synapses
Axon initial segment
Extrasynaptic receptors
Describe how the Axon Initial Segment can be modulated by GABA
GABA can shut the transmission of the AIS down so that the axon does not fire despite dendritic activity
What is the difference between tonic and phasic signalling, and what causes either?
Phasic: one large leak that drops off, caused by extrasynaptic GABA flooding the synapse and out-competing glial cells in terms of spillover
Tonic: Low but constant GABA levels cause a steady signal
