Rapid Chemically Induced Changes of PtdIns(4,5)P 2 Gate KCNQ Ion Channels

• DOI: 10.1126/science.1131163
• Publication Date: 2006-09-22T00:57:35Z
• Authors: Byung-Chang Suh; Takanari Inoue; Tobias Meyer; Bertil Hille
• Keywords: Phosphatidylinositol 4,5-Diphosphate; 0301 basic medicine; KCNQ Potassium Channels; Oxotremorine; Recombinant Fusion Proteins; Cell Membrane; Inositol Polyphosphate 5-Phosphatases; Second Messenger Systems; Phosphoric Monoester Hydrolases; Cell Line; KCNQ3 Potassium Channel; Diglycerides; Mice; 03 medical and health sciences; NIH 3T3 Cells; Animals; Humans; KCNQ2 Potassium Channel; Calcium; Phosphorylation; Dimerization; Ion Channel Gating

To resolve the controversy about messengers regulating KCNQ ion channels during phospholipase C–mediated suppression of current, we designed translocatable enzymes that quickly alter the phosphoinositide composition of the plasma membrane after application of a chemical cue. The KCNQ current falls rapidly to zero when phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 or PI(4,5)P 2 ] is depleted without changing Ca 2+ , diacylglycerol, or inositol 1,4,5-trisphosphate. Current rises by 30% when PI(4,5)P 2 is overproduced and does not change when phosphatidylinositol 3,4,5-trisphosphate is raised. Hence, the depletion of PI(4,5)P 2 suffices to suppress current fully, and other second messengers are not needed. Our approach is ideally suited to study biological signaling networks involving membrane phosphoinositides.