Regulation of the temperature-dependent activation of Transient Receptor Potential Vanilloid 1 by phospholipids in planar lipid bilayers [Molecular Biophysics]

January 5th, 2015 by Sun, X., Zakharian, E.

The Transient Receptor Potential Vanilloid 1 (TRPV1) channels are heat-activated non-selective cation channels. TRPV1 channels are polymodal in their function and exhibit multi-faceted regulation with various molecular compounds. In this regard, phosphoinositides, particularly phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol-4- phosphate (PI(4)P), 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 PI(4,5)P2, TRPV1 channels demonstrated rapid activation in the temperature range between 33-39 C and achieved full channel opening at 42 C. In this temperature range, TRPV1 heat activation exhibited steep temperature dependence (temperature coefficient, Q10, of 18.3), and the channel openings were accompanied by large changes in entropy and enthalpy, suggesting a substantial conformation change. In the similar temperature range, another phosphoinositide PI(4)P also potentiated heat activation of TRPV1, however, with much lower efficiency. Negatively charged phosphatidylglycerol (POPG) could also induce heat activation of TRPV1 channels, although to a small conductance state. Our data demonstrate that phospholipids, specifically phosphoinositides, are important regulators of TRPV1 and are required for the heat-induced channel activity.
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