K(ATP) channels: linker between phospholipid metabolism and excitability

Abstract

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.