Identification of a domain within S1 that enhances modulation by cyclothiazide. a, Schematic representation of the structure of the agonist-binding domain, focusing on β-strands 7 and 8 and α-helices J and K, also shown in Figure 1.b, Electrophysiological responses (bottom) of chimeric receptors expressed inXenopus oocytes, with schematic representations (top) of the chimeric constructs (GluR1 sequences shown in black; GluR6 sequences shown in gray). Control glutamate and kainate responses (hairline) are superimposed on responses in the presence of cyclothiazide (CTZ; bold). Closed arrowspoint to the peak current in the control; open arrowspoint to the peak current in the presence of cyclothiazide. Wild-type (wt) GluR1 currents were potentiated by cyclothiazide (b₁), whereas wt GluR6 currents were consistently inhibited by cyclothiazide (b₂ ). GluR6-Q₇₅₅S currents were somewhat potentiated by cyclothiazide (Partin et al., 1995) (b₃ ), but the double chimera GluR6-BETA 7,8 + Q₇₅₅S was strongly potentiated by cyclothiazide (b₄ ). Insets (b₄), A higher magnification of control currents for GluR6-BETA 7,8 + Q₇₅₅S. These experiments were done in the absence of Concanavalin A, a modulator of kainate receptor desensitization, and therefore the responses to agonists desensitized within 1–2 sec in oocytes. c, The mean potentiation by 100 μmCTZ of peak currents (I_AGONIST+CTZ/I_AGONIST) plotted for 300 μm glutamate (stippled bars) or 300 μm kainate (filled bars). Error bars represent SEM; the number of oocytes studied under each condition ranges from 5 to 10.