Phosphatidylinositol‐4,5‐bisphosphate, PIP 2 , controls KCNQ1/KCNE1 voltage‐gated potassium channels: a functional homology between voltage‐gated and inward rectifier K + channels

Phosphatidylinositol‐4,5‐bisphosphate (PIP 2 ) is a major signaling molecule implicated in the regulation of various ion transporters and channels. Here we show that PIP 2 and intracellular MgATP control the activity of the KCNQ1/KCNE1 potassium channel complex. In excised patch–clamp recordings, the KCNQ1/KCNE1 current decreased spontaneously with time. This rundown was markedly slowed by cytosolic application of PIP 2 and fully prevented by application of PIP 2 plus MgATP. PIP 2 ‐dependent rundown was accompanied by acceleration in the current deactivation kinetics, whereas the MgATP‐dependent rundown was not. Cytosolic application of PIP 2 slowed deactivation kinetics and also shifted the voltage dependency of the channel activation toward negative potentials. Complex changes in the current characteristics induced by membrane PIP 2 was fully restituted by a model originally elaborated for ATP‐regulated two transmembrane‐domain potassium channels. The model is consistent with stabilization by PIP 2 of KCNQ1/KCNE1 channels in the open state. Our data suggest a striking functional homology between a six transmembrane‐domain voltage‐gated channel and a two transmembrane‐domain ATP‐gated channel.