Figure 1

Selective binding of TAK-653 to AMPA-R in a glutamate-dependent manner. (A) Chemical structure of TAK-653 and TAK-137. (B) The GluA2 (flop)/glutamate/TAK-653 complex crystallized as a dimer. (C) Displacement studies with TAK-653 using the SPA assay with [³H]-HBT1 and His-LBD. Data are represented as mean ± SD (n = 4). (D) Effects of glutamate on the binding of [³H]-TAK-653 to His-LBD. Data are represented as relative value ± SD in counts per minute (CPM) (n = 3). (E) Effect of TAK-653 on the binding of [³H]-AMPA to His-LBD. Data are represented as mean ± SEM (n = 4). (F) Effects of TAK-653 on Ca²⁺ influx in GluA1i CHO cells in the presence (open circle) and absence (open square) of 3 mM glutamate. Data are represented as mean ± SD (n = 3). (G) Effects of TAK-653 on Ca²⁺ influx in CHO cells expressing GluA1i WT or GluA1i S743A in the absence or presence of glutamate (0.3 μM, 1 μM and 3 mM). S743 in GluA1i LBD corresponds to S750 in GluA2o LBD. Data are represented as mean ± SD (n = 3). (H) Effects of TAK-653 on Ca²⁺ influx in hGluA1i CHO cells (closed circle) and rGluA1i CHO cells (open circle) in the presence of 3 mM glutamate. Data are represented as mean ± SD (n = 3).