PIP2 AND PIP AS DETERMINANTS FOR ATP INHIBITION OF K-ATP CHANNELS

Adenosine triphosphate (ATP)-sensitive potassium (K-ATP) channels coup le electrical activity to Cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of K-ATP channels varies among t issues and is affected by the metabolic and regulatory state of indivi dual cells, suggesting involvement of endogenous factors. It is report ed here that phosphatidylinositol-4,5-bisphosphate (PIP2) and phosphat idylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned K-A TP 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 magnitud e. Receptor-mediated activation of phospholipase C resulted in inhibit ion of K-ATP-mediated currents. These results represent a mechanism fo r control of excitability through phospholipids.