Fig. 7.

Hypothesis for the stabilization of the KCNQ channel by PIP₂ and intracellular zinc. (A) An active channel in the presence of a saturating PIP₂ concentration. (B) A channel inhibited by PIP₂ depletion (e.g., because of PLC or ciVSP activation). (C) A channel in the absence of membrane PIP₂ but stabilized by zinc, e.g., via shielding the negatively charged residues and coordinating the channel–membrane interface to strengthen the interactions with other phospholipids. (D) A scenario of a subsaturating membrane PIP₂ level when the channel activity is maximized by zinc because of the increased stability of the interaction with PIP₂ and other membrane phospholipids.