Figure 4.
Channel block of GluA2-containing AMPARs by PhTx-74 depends on agonist efficacy. A, Representative traces demonstrating block by 100 μm PhTx-74 of currents evoked by ultrafast application of 1 mm kainate, at a holding potential of −60 mV, onto outside-out patches from HEK293T cells expressing GluA2/A4 AMPARs alone (left), GluA2/A4 with γ-2 (middle), and GluA2/A4 with γ-8 (right). The rate and extent of PhTx-74 block of kainate-evoked current is enhanced in the presence of TARPs. B, Bar graph comparing the percentage block by 100 μm PhTx-74 of kainate-evoked (open bars) and glutamate/CTZ-evoked (gray bars; data from Fig. 2D, left) currents from HEK293T cells expressing GluA2/A4 AMPARs alone and coexpressed with γ-2 and γ-8 (n = 7–10). For kainate-evoked currents, asterisks denote significance versus GluA2/A4 (**p < 0.005 for both γ-2 and γ-8), and hash marks denote significance versus GluA2/A4 + γ-2 (#p < 0.05). For GluA2/A4 AMPARs alone and with γ-2, percentage block was greater with glutamate/CTZ compared with kainate (§p < 0.05; §§§p < 0.0001). Error bars denote ±SEM.