Regulation of TRPV1 Ion Channel by Phosphoinositide (4,5)-Bisphosphate

Abstract

Background: Whether phosphoinositide 4,5-bisphosphate (PI(4,5)P 2) activates or inhibits TRPV1 is controversial. Results: PI(4,5)P2 in the intracellular leaflet activates TRPV1, whereas PI(4,5)P2 in the extracellular leaflet inhibits TRPV1. Conclusion: Inhibition by PI(4,5)P2 in the extracellular leaflet may explain previous findings that TRPV1 reconstituted into PI(4,5)P2-containing liposomes is inhibited. Significance: PI(4,5)P2 in the physiologically relevant leaflet (the intracellular leaflet) of the membrane activates TRPV1. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.