Fig. 4.

A simplified chemomechanical gating scheme of SK/IK channels that was adapted from a previous report [2]. The first step in channel activation is Ca²⁺ binding to CaM. Next, PIP₂ mediates mechanical coupling into the opening of the channel pore. For simplicity, only the S6 transmembrane domains from two channel subunits are shown. The N-lobe of CaM is in red, while the C-lobe of CaM is in blue. PIP₂ is shown in cyan. Ca²⁺ ions are shown as gray dots. Positive SK/IK channel modulators (e.g., NS309 or 1-EBIO) can enhance the mechanical coupling of Ca²⁺ binding into the channel opening. Conversely, phosphorylation of CaM by casein kinase 2 can negatively modulate the PIP₂-mediated mechanical coupling.