Rapid Chemically Induced Changes of PtdIns(4,5)P₂ Gate KCNQ Ion Channels

• Published in: Science (American Association for the Advancement of Science) Vol. 314; no. 5804; pp. 1454 - 1457
• Main Authors: Suh, Byung-Chang, Inoue, Takanari, Meyer, Tobias, Hille, Bertil
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 01.12.2006; The American Association for the Advancement of Science
• Subjects: Animals; Calcium; Calcium - metabolism; Cell Line; Cell Membrane - metabolism; Cell membranes; Cytosol; Diglycerides - metabolism; Dimerization; Enzymes; Fluorescence; Humans; Inositol Polyphosphate 5-Phosphatases; Inositols; Ion Channel Gating; Ion channels; Ions; KCNQ Potassium Channels - metabolism; KCNQ2 Potassium Channel - metabolism; KCNQ3 Potassium Channel - metabolism; Mice; NIH 3T3 Cells; Oxotremorine - analogs & derivatives; Oxotremorine - pharmacology; Phosphatidylinositol 4,5-Diphosphate - metabolism; Phosphatidylinositols; Phosphoric Monoester Hydrolases - metabolism; Phosphorylation; Plasma currents; Recombinant Fusion Proteins - metabolism; Second Messenger Systems; Signal transduction; Sirolimus - analogs & derivatives; Sirolimus - pharmacology
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1131163

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)P₂ or PI(4,5)P₂] is depleted without changing Ca²⁺, diacylglycerol, or inositol 1,4,5-trisphosphate. Current rises by 30% when PI(4,5)P₂ is overproduced and does not change when phosphatidylinositol 3,4,5-trisphosphate is raised. Hence, the depletion of PI(4,5)P₂ 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.