Mechanism of inhibition of the GluA1 AMPA receptor channel opening by the 2,3-benzodiazepine compound GYKI 52466 and a N-methyl-carbamoyl derivative.

ABSTRACT: 2,3-Benzodiazepine derivatives, also known as GYKI compounds, represent a group of the most promising synthetic inhibitors of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Here we investigate the mechanism of inhibition of the GluA1 channel opening and the site of inhibition by GYKI 52466 and its N-3 methyl-carbamoyl derivative, which we term as BDZ-f. GluA1 is a key AMPA receptor subunit involved in the brain function. Excessive activity and elevated expression of GluA1, however, has been implicated in a number of neurological disorders. Using a laser-pulse photolysis technique, which provides ∼60 μs resolution, we measured the effect of these inhibitors on the rate of GluA1 channel opening and the amplitude of the glutamate-induced whole-cell current. We found th

SUBMITTER: Wu A 

PROVIDER: S-EPMC4025570 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature