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Thomas Baukrowitz,* Uwe Schulte,* Dominik Oliver, Stefan Herlitze, Tobias Krauter, Stephen J. Tucker, J. Peter Ruppersberg, Bernd Fakler^
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple electrical activity to cellular metabolism through their inhibition by intracellular ATP. ATP inhibition of K^sub 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,) and phosphatidylinositol-4-phosphate (PIP) controlled ATP inhibition of cloned K^sub ATP^ channels (K^sub ir^6.2 and SUR1). These phospholipids acted on the K^sub ir^6.2 subunit and shifted ATP sensitivity by several orders of magnitude. Receptor-mediated activation of phospholipase C resulted in inhibition of K^sub ATP^mediated currents. These results represent a mechanism for control of excitability through phospholipids.
The observation that a metabotropic receptor coupling to PLC can control activity of K^sub ATP^ channels might point toward the physiological role of the phospholipid effect presented here. This role is supported by the finding that ATP sensitivity of cardiac KATP channels is regulated through a G-proteinrelated pathway (22). This was observed in a membrane patch and did not involve a diffusible second messenger. Thus, phospholipidmediated opening of otherwise ATP-blocked K^sub ATP^ channels might represent a new mechanism to control excitability in a wide variety of cells.
References and Notes
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