Identification of an Inhibitory Alcohol Binding Site in GABAaRho1

Abstract

Ionotropic glutamate receptors are believed to undergo twisting and shortening upon activation. We used fast-scan atomic force microscopy (AFM) imaging to examine the conformational change of the GluK2 kainate receptor, integrated into a lipid bilayer, in response to activation by the agonist glutamate, either added to the imaging chamber or generated by UV photolysis of caged glutamate. In both cases, the height of the extracellular domain of the receptor fell by 0.8 nm upon activation. In contrast, there was no significant height change in response to glutamate in the presence of the GluK2 antagonist CNQX. Our study represents the first demonstration of the effect of activation on the conformation of GluK2 receptors under near-physiological conditions.