Cyclothiazide potentiates agonist responses at human AMPA/kainate receptors expressed in oocytes

Cloned human AMPA/kainate subunits were functionally expressed in Xenopus oocytes. Cyclothiazide potentiated kainate-evoked currents by 682 +/- 122% (mean +/- S.E.M., n = 5), 1396 +/- 55% (n = 4), and 690 +/- 40% (n = 14) in oocytes expressing GluR1, GluR2, and GluR1 + GluR2 receptors, respectively. AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate)-induced currents were also potentiated by cyclothiazide. GYKI 52466 (1-(4-amino-phenyl)-4-methyl-7,8-methylendioxyl-5H-2,3-benzod++ + iazepine hydrochloride) attenuated cyclothiazide potentiation in all cases. Thus, modulatory sites for cyclothiazide and GYKI 52466 exist on individual human AMPA/kainate receptor subunits. Additionally, kainate appears to act as a desensitizing partial agonist at human GluR1 and GluR2 receptor subunits.