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

Abstract

Adenosine triphosphate (ATP)–sensitive potassium (K ATP ) channels couple electrical activity to cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of K ATP 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 (PIP 2 ) and phosphatidylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned K ATP channels (K ir 6.2 and SUR1). These phospholipids acted on the K ir 6.2 subunit and shifted ATP sensitivity by several orders of magnitude. Receptor-mediated activation of phospholipase C resulted in inhibition of K ATP -mediated currents. These results represent a mechanism for control of excitability through phospholipids.