Suggested model for M-type Kv7.2/7.3 channel activation by binding of PI(4,5)P2 molecules. (A) Cartoon of an M-type potassium channel composed of two Kv7.2 and two Kv7.3 subunits arranged alternately around a central ion channel. Each subunit contains both voltage-sensing and pore-forming domains, as illustrated on the right, as well as a putative PI(4,5)P2 binding region located within the C-terminal domain. (B) Model scheme of PI(4,5)P2 binding and channel gating assuming that PI(4,5)P2 binds independently to each subunit and that channels can gate to the open state (denoted by asterisks) when both Kv7.3 (Q3) subunits have bound PI(4,5)P2 (Q2P2Q3), when both Kv7.3 subunits and one Kv7.2 (Q2) subunit are occupied (PQ2P2Q3), or when all four subunits are occupied (P2Q2P2Q3). The equilibrium dissociation constants for PI(4,5)P2 binding to Kv7.3 (K3 = k−3/k+3) and Kv7.2 (K2 = k−2/k+2) subunits and the equilibrium constants describing channel gating to each open state—E1(β1/α1), E2(β2/α2), and E3(β3/α3)—are determined by their respective rate constants, as indicated.
