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. 2020 Jun 23;11:583. doi: 10.3389/fphys.2020.00583

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Copyright © 2020 Abbott.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Models of GABA and PIP₂ signaling in KCNQ and KCNQ2/3–SMIT1 complexes. (A) Cartoon showing lack of communication between the KCNQ VSD and pore in the absence of PIP₂. (B) Cartoon showing voltage-dependent activation of KCNQs in the presence of PIP2. (C) Cartoon showing hypothetical GABA-induced KCNQ activation in the absence of PIP₂. (D) Cartoon showing hypothetical GABA-induced KCNQ activation in the presence of PIP₂. (E) Cartoon of KCNQ2/3–SMIT1 interactions showing the functional consequences of physical interaction and modulation by small molecules. DAG, diacylglycerol; G6P, glucose-6-phosphate; IMPase, inositol monophosphatase; IP, inositol phosphate; inositol polyphosphatase 1-phosphatase; MI, myo-inositol; PI4K, phosphatidylinositol 4-kinase; PI5K, phosphatidylinositol-5 kinase; PLC, phospholipase C. From Manville and Abbott (2020b) with permission.