Figure 7.
Use of a subunit-specific model to predict the Popen of Kv7.2/7.3 channels. (A and B) Illustration of fitting of the model (solid lines), depicted in Fig. 6, to the steady-state open probability of Kv7.2/7.3 channels and Kv7.2/Kv7.3(EEE) mutant channels activated by DiC8-PI(4,5)P2. The fitted lines correspond to the parameter values given in Table 1 (data points show mean ± SEM; Kv7.2/Kv7.3, n = 20–49 patches; Kv7.2/Kv7.3(EEE), n = 8–13 patches). (C and D) Computed contribution of each of the open states (Po1, Po2, and Po3) to the overall channel Popen. The model predicts that at low DiC8-PI(4,5)P2 concentrations, most channel openings result from binding of DiC8-PI(4,5)P2 to the Kv7.3 subunits, which peaks around 7 µM at 0.145 (dotted lines), whereas combined binding to both Kv7.3 and Kv7.2 subunits (dashed lines) underlies the steepening of the Popen curve and the high open probabilities observed at high DiC8-PI(4,5)P2 concentrations. In contrast, mutant Kv7.2/Kv7.3(EEE) channels are weakly activated by DiC8-PI(4,5)P2, with a maximum open probability for channels with both Kv7.3 binding sites occupied (Po3) of 0.027 occurring at 10 µM DiC8-PI(4,5)P2.