Time-resolved photolabeling of the nicotinic acetylcholine receptor by [3H]azietomidate, an open-state inhibitor.

ABSTRACT: Azietomidate is a photoreactive analog of the general anesthetic etomidate that acts as a nicotinic acetylcholine receptor (nAChR) noncompetitive antagonist. We used rapid perfusion electrophysiological techniques to characterize the state dependence and kinetics of azietomidate inhibition of Torpedo californica nAChRs and time-resolved photolabeling to identify the nAChR binding sites occupied after exposure to [(3)H]azietomidate and agonist for 50 ms (open state) or at equilibrium (desensitized state). Azietomidate acted primarily as an open channel inhibitor characterized by a bimolecular association rate constant of k(+) = 5 x 10(5) M(-1) s(-1) and a dissociation rate constant of <3s(-1). Azietomidate at 10 microM, when perfused with acetylcholine (ACh), inhibited the ACh response by a

SUBMITTER: Chiara DC 

PROVIDER: S-EPMC2672814 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature