PIP 2 and PIP as Determinants for ATP Inhibition of K ATP Channels

作者：Thomas Baukrowitz, Uwe Schulte, Dominik Oliver, Stefan Herlitze, Tobias Krauter, Stephen J. Tucker, Johann Peter Ruppersberg, Bernd Fakler · 发表于：Science · 年份：1998 · DOI：10.1126/science.282.5391.1141 · 被引用次数：523 · 研究领域：Ion channel regulation and function、Cardiac electrophysiology and arrhythmias、Cardiac Ischemia and Reperfusion

Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple electrical activity to cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of KATP channels varies among tissues and is affected by the metabolic and regulatory state of individual cells, suggesting involvement of endogenous factors. It is reported here that phosphatidylinositol-4, 5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned KATP channels (Kir6.2 and SUR1). These phospholipids acted on the Kir6.2 subunit and shifted ATP sensitivity by several orders of magnitude. Receptor-mediated activation of phospholipase C resulted in inhibition of KATP-mediated currents. These results represent a mechanism for control of excitability through phospholipids.