Figure 3.

Model for KCNQ1 gating

A, representative K⁺ current families for KCNQ1 (stepping from a holding voltage of –80 mV to test voltages from –80 to +60 mV in 10 mV increments. Tail voltage is –30 mV), KCNQ1–KCNE1 (stepping from a holding voltage of –80 mV to test voltages from –110 to +60 mV in 10 mV increments. Tail voltage is –30 mV), and KCNQ1–KCNE3 (stepping from a holding voltage of –100 mV to test voltages from –100 to +60 mV in 20 mV increments. Tail voltage is –40 mV). B, ten-state model with five closed states (C₀–C₄) and five open states (O₀–O₄), where subscript depicts the number of activated S4s. Horizontal transitions are independent activation of S4s and vertical transition is the opening of the gate (with a potential extra concerted movement of all four S4s; Barro-Soria et al. 2014). Suggested transitions for KCNQ1 alone (red dashed lines), KCNQ1–KCNE1 (blue dashed line), and KCNQ1–KCNE3 (magenta dashed line) in response to a depolarization. Even at very negative voltages (all S4s down), KCNQ1 expressed alone displays a significant open probability that increases with more activated S4s (Osteen et al. 2012). In response to a depolarization, most KCNQ1 channels open after one or two S4s have activated (thicker red dashed lines). In contrast, KCNQ1–KCNE1 only opens after all four S4s have activated (all four S4s up; Barro-Soria et al. 2014), whereas in KCNQ1–KCNE3 the S4s are always activated independently of voltage and channel opening is relatively voltage independent (Nakajo & Kubo, 2007; Rocheleau & Kobertz, 2008).