K(ATP) channels: linker between phospholipid metabolism and excitability.
ATP-sensitive potassium (K(ATP)) channels couple electrical activity to cellular metabolism via their inhibition by intracellular ATP. When examined in excised patches, ATP concentrations required for half-maximal inhibition (IC(50)) varied among tissues and were reported to be as low as 10 microM. This set up a puzzling question on how activation of K(ATP) channels can occur under physiological conditions, where the cytoplasmic concentration of ATP is much higher than that required for channel inhibition. A new twist was added to this puzzle when two recent reports showed that phospholipids such as phosphatidylinositol-4,5-bisphosphate (PIP(2)) and phosphatidyl-4-phosphate (PIP) are able to shift ATP-sensitivity of K(ATP) channels from the micro- into the millimolar range and thus provide a mechanism for physiological activation of the channels. This commentary describes how phospholipids control ATP inhibition of K(ATP) channels and how this mechanism is regulated effectively by receptor-mediated stimulation of phospholipase C.
Baukrowitz
T
T
Department of Physiology II, University of Tübingen, Germany.
Fakler
B
B
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D015221:Potassium Channels; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2; D010738:Type C Phospholipases / Q000378:metabolism
D008565:Membrane Proteins; C546385:P2RY2 protein, human; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D015221:Potassium Channels; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C117780:mitochondrial K(ATP) channel; C037178:phosphatidylinositol 4-phosphate; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases