PIP2 and PIP as determinants for ATP inhibition of KATP channels.
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.
Baukrowitz
T
T
Department of Physiology II, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
Schulte
U
U
Oliver
D
D
Herlitze
S
S
Krauter
T
T
Tucker
S J
SJ
Ruppersberg
J P
JP
Fakler
B
B
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003001:Cloning, Molecular; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D009154:Mutation; D009865:Oocytes; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism / Q000494:pharmacology*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D064233:Sulfonylurea Receptors; D010738:Type C Phospholipases / Q000378:metabolism; D014982:Xenopus laevis
D018528:ATP-Binding Cassette Transporters; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; D011993:Recombinant Fusion Proteins; D064233:Sulfonylurea Receptors; C037178:phosphatidylinositol 4-phosphate; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D003981:Diazoxide