Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels.
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.
Suh
Byung-Chang
BC
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA.
Inoue
Takanari
T
Meyer
Tobias
T
Hille
Bertil
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D015640:Ion Channel Gating; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D051658:KCNQ2 Potassium Channel / Q000378:metabolism; D051659:KCNQ3 Potassium Channel / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015290:Second Messenger Systems; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology
D004075:Diglycerides; D051656:KCNQ Potassium Channels; D051658:KCNQ2 Potassium Channel; D051659:KCNQ3 Potassium Channel; D019269:Phosphatidylinositol 4,5-Diphosphate; D011993:Recombinant Fusion Proteins; D010095:Oxotremorine; C042743:oxotremorine M; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D002118:Calcium; D020123:Sirolimus