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 GluR(1), GluR(2), and GluR(1) + GluR(2) 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 GYKI52466 exist on individual human AMPA/kainate receptor subunits. Additionally, kainate appears to act as a desensitizing partial agonist at human GluR(1) and GluR(2) receptor subunits.