Figure 1. Model of 3‐step rearrangement of AKAP–KCNQ channel complex .

See Kosenko et al. (2012) and Kosenko & Hoshi (2013). AKAP79/150 organizes a signalling complex at the carboxyl terminus of KCNQ channels, including PKC and CaM. Stable KCNQ–CaM association is required for maintaining tonic PIP₂ affinity. Stimulation of G_q/11‐coupled muscarinic receptors depletes PIP₂ and activates AKAP79/150‐anchored PKC, which phosphorylates KCNQ subunits near the CaM binding sites of KCNQ channels. PKC phosphorylation, or ${\mathrm{Ca}}_{\mathrm{i}}^{2+}$ signals, triggers CaM conformational changes and/or dissociation from the cytoplasmic tail of KCNQ channels, resulting in lowered PIP₂ affinity and suppressed channel activity. AKAP79/150 may act as an acceptor to bind to dissociated CaM. Thus, together with PIP₂ depletion, receptor stimulation suppresses KCNQ channel activity by inducing CaM rearrangement and dissociation from the channel complex. Note that the depression of M‐current by reducing channel opening is schematically indicated here by a squeezing together of the two halves of the channel, and a thinning of the directional arrow of potassium flux. See the text for issues concerning this model.