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)P-2, 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.