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

Xiaona Du,Xuan Zhang,Xingjuan Chen,Xian Geng,Caixia Jia,Hailin Zhang

doi:10.1074/jbc.m109.068205

Abstract

A growing body of evidence shows that membrane phosphatidylinositol 4,5-bisphosphates (PtdIns(4,5)P(2), PIP(2)) play an important role in cell signaling. The presence of PIP(2) 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. PIP(2) levels in the membrane are dynamically modulated, which is an important signaling mechanism for modulation of PIP(2)-dependent cellular processes. In this study, we describe a novel mechanism of membrane PIP(2) modulation. Membrane depolarization induces an elevation in membrane PIP(2), and subsequently increases functions of PIP(2)-sensitive KCNQ potassium channels expressed in Xenopus oocytes. Further evidence suggests that the depolarization-induced elevation of membrane PIP(2) occurs through increased activity of PI4 kinase. With increased recognition of the importance of PIP(2) in cell function, the effect of membrane depolarization in PIP(2) metabolism is destined to have important physiological implications.

Highlights

Among the targets of PIP2 signaling, ion channels have been the focus of recent studies
Membrane Depolarization Augments the Amplitude but Does Not Affect the Kinetics of KCNQ2/Q3 Currents Expressed in Xenopus Oocytes—The heterologous currents of KCNQ2 and KCNQ3 Kϩ channels are believed to be the major components of neuronal M currents
We noticed that when expressed in Xenopus oocytes, the amplitudes of KCNQ2/Q3 currents activated by a depolarizing voltage always increased with time (Fig. 1A)

Summary

Introduction

Among the targets of PIP2 signaling, ion channels have been the focus of recent studies. The membrane depolarization elevates membrane PIP2 levels and enhances PIP2-dependent KCNQ2/Q3 currents expressed in Xenopus oocytes. The depolarization-induced elevation of PIP2 levels is a result of increased activity of PI4 kinase.

Results

Conclusion