title: Regulation of the temperature-dependent activation of transient receptor potential vanilloid 1 (TRPV1) by phospholipids in planar lipid bilayers.
abstract: TRPV1 (transient receptor potential vanilloid 1) proteins are heat-activated nonselective cation channels. TRPV1 channels are polymodal in their function and exhibit multifaceted regulation with various molecular compounds. In this regard, phosphoinositides, particularly phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate, are important channel regulators. However, their effects on TRPV1 channel activity have not been conclusively determined. To characterize temperature-induced activation of TRPV1 in the presence of different phospholipids, we purified the TRPV1 protein from HEK-293 cells and incorporated it into planar lipid bilayers. In the presence of 2.5 μm phosphatidylinositol 4,5-bisphosphate, TRPV1 channels demonstrated rapid activation at 33-39 °C and achieved full channel opening at 42 °C. At this temperature range, TRPV1 heat activation exhibited steep temperature dependence (temperature coefficient (Q10) of 18), and the channel openings were accompanied by large changes in entropy and enthalpy, suggesting a substantial conformation change. At a similar temperature range, another phosphoinositide, phosphatidylinositol 4-phosphate, also potentiated heat activation of TRPV1, but with much lower efficiency. Negatively charged phosphatidylglycerol could also induce heat activation of TRPV1 channels, although with a small-conductance state. Our data demonstrate that phospholipids, specifically phosphoinositides, are important regulators of TRPV1 and are required for heat-induced channel activity.
authors.affiliation: From the Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, Illinois 61605.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Sun
authors.affiliation: From the Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, Illinois 61605. Electronic address: zakharel@uic.edu.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zakharian
mesh_terms: D057809:HEK293 Cells; D006358:Hot Temperature; D006801:Humans; D015640:Ion Channel Gating; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D010743:Phospholipids; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human
keywords: Calcium Channel; Inositol Phospholipid; Ion Channel; Lipid Bilayer; Phosphoinositide; Thermodynamics; Transient Receptor Potential Channels (TRP Channels)