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Originally published in Science Express on 21 September 2006
Science 1 December 2006:
Vol. 314. no. 5804, pp. 1454 - 1457
DOI: 10.1126/science.1131163
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Reports

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

Byung-Chang Suh,1* Takanari Inoue,2* Tobias Meyer,2 Bertil Hille1{dagger}

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.

1 Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA.
2 Department of Molecular Pharmacology, Stanford University, Clark Center, 318 Campus Drive, Stanford, CA 94305, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: hille{at}u.washington.edu

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