Depolarization Increases Phosphatidylinositol (PI) 4,5-Bisphosphate Level and KCNQ Currents through PI 4-Kinase Mechanisms

A growing body of evidence shows that membrane phosphatidylinositol 4,5-bisphosphates (PtdIns(4,5)P², PIP²) play an important role in cell signaling. The presence of PIP² is fundamentally important for maintaining the functions of a large number of ion channels and transporters, and for other cell processes such as vesicle trafficking, mobility, and endo- and exocytosis. PIP² levels in the membrane are dynamically modulated, which is an important signaling mechanism for modulation of PIP²-dependent cellular processes. In this study, we describe a novel mechanism of membrane PIP² modulation. Membrane depolarization induces an elevation in membrane PIP², and subsequently increases functions of PIP²-sensitive KCNQ potassium channels expressed in Xenopus oocytes. Further evidence suggests that the depolarization-induced elevation of membrane PIP² occurs through increased activity of PI4 kinase. With increased recognition of the importance of PIP² in cell function, the effect of membrane depolarization in PIP² metabolism is destined to have important physiological implications.