Picrotoxin is a noncompetitive antagonist of GABAA receptors

Picrotoxin is a non-competitive antagonist of GABA_A receptors. What is the most likely site of action of picrotoxin?

Solution

The site at which picrotoxin binds is only accessible from the external side of the membrane because cytoplasmic application of picrotoxin had no effect on GABA-inducedcurrents. Which implies that the picrotoxin binding site is most likely on the water accessible surface of the protein and that the site is not accessible from the lipid-protein interface, where the sidedness of application should not matter.