Case 5 Flashcards
What type of receptor is a GABA-A receptor?
Ligand gated ion channel
What ion does GABA-A receptor use to bring about its affects?
Chloride Cl-
What endogenous ligand acts on GABA-A receptors?
GABA
What does GABA do?
Plays a critical role in inhibitory transmission
How many subunits make up a GABA-A receptor?
5 subunits
What are the 5 subunits that make up the GABA-A receptor?
Could be:
2x alpha 1-6 (α)
2x Beta 1-3 (β)
and either 1x Gamma (γ) 1-3 or Delta (δ) or Epsilon (ε) or Pi (π) or Theta (θ) or Rho (ρ)
What is the commonest subunit form human of GABA-A receptor?
2x alpha (α) 2X Beta (β) 1x Gamma (γ)
What is the form of BDZ-sensitive GABA-A receptor?
2x alpha (α) 1,2,3 (not 4,5,6)* 2x Beta (β) 1x Gamma (γ) 2 or 3 (not 1)*
What is the form of BDZ-insensitive GABA-A receptor?
2x alpha (α) 4 or 6 (not 1,2,3,5)* 2x Beta (β) 1x Delta (δ)
With regards to the BDZ-sensitive GABA-A receptor: what is it sensitive for?
Benzodiazepines
With regards to any GABA-A receptor: where does GABA bind?
between alpha (α) and Beta (β) subunits at the top, and bottom left always.
How many GABA molecules can bind to a GABA-A receptor in general?
only 2!
With regards to the BDZ-sensitive GABA-A receptor: do BDZ’s bind in the same site as GABA?
NO they do not bind at the GABA binding site.
Therefore are not “direct” antagonists.
They bind to separate allosteric site.
Therefore called positive allosteric molecules (PAM’s)
With regards to the BDZ-sensitive GABA-A receptor: How many molecules of BDZ’s can bind?
only 1
With regards to the BDZ-sensitive GABA-A receptor: between which subunits do BDZ’s bind?
between alpha (α) 1,2,3 and Gamma (γ) 2 or 3
Can BDZ’s elicit their effects without the presence of GABA?
No GABA needs to be present and bound to receptor.
Why and how are “Z-drugs” different to BDZ’s. Refer to function on receptor and subunits.
(What are Z drugs selective for - effects, and what are BDZ drugs selective for - effects)
Z-drugs are alpha (α) 1 selective, and therefore hypnotics.
BDZ’s are non alpha (α) selective (i.e. bind to 1,2,3) and so give sedative* effects as well as anxiolytics*.
There are no selective BDZ’s available.
With regards to the BDZ-insensitive GABA-A receptor: what is it sensitive for?
Neurosteroids
Alcohol
General Anaesthetics
With regards to the BDZ-insensitive GABA-A receptor: where do Alcohol/Neurosteroids/GA’s bind?
between alpha (α) 4 or 6 and Delta (δ)
With regards to GABA-A receptors: What does alpha (α) 1 regulate? and what do alpha (α) 2,3 regulate?
i.e. what do they do
alpha (α) 1: regulates sleep
alpha (α) 2 or 3: regulates anxiety
What are barbiturates?
They are an old school BDZ.
CNS depressants, sedatives, anxiolytics, muscle relaxants, anticonvulsants, addictive!
Where can barbiturates bind to?
They have multiple binding pockets. Between Beta (β) and Gamma (γ) or alpha (α)/ Gamma (γ)
Do barbiturates bind to the same binding sites as BDZ’s?
No, distinct binding sites.
Are barbiturates also PAM’s? What is a PAM anyway?
Yes they are PAM’s.
Stands for Positive Allosteric Modulators.
