Affiliation:
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.
Abstract
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.
Publisher
American Association for the Advancement of Science (AAAS)
Cited by
435 articles.
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