Regulation of the Temperature-dependent Activation of Transient Receptor Potential Vanilloid 1 (TRPV1) by Phospholipids in Planar Lipid Bilayers

Abstract

Background: Regulation of the temperature-dependent activity of TRPV1 channels with phosphoinositides is not well understood. Results: Phosphoinositides directly facilitate heat activation of TRPV1 reconstituted in neutral planar lipid bilayers. Different anionic lipids evoke TRPV1 channel activity with distinct open probability and conductance states. Conclusion: Phospholipids are required for heat-induced activation of TRPV1. Significance: Phosphoinositides are essential regulators of TRPV1 gating.

Phosphoinositide regulation of TRPV1 revisited

“…5D) [65]. In a subsequent paper it was shown that PG could also support heat-induced TRPV1 activity in planar lipid bilayers in a lipid mixture of PG:PC:PE = 3:3:1 with high open probability, but lower unitary conductance [114]. …”

“…Since then, several reviews on more general topics discussed phosphoinositide regulation of TRPV1 [29, 40, 78, 95, 96]. Due to the unceasing interest and recent developments in this controversial topic [8, 65, 66, 84, 105, 114], however, I felt that a comprehensive and specific discussion is warranted on phosphoinositide regulation of TRPV1.…”

“…Here I will summarize the literature, critically discuss the experiments supporting the dependence of TRPV1 activity on phosphoinositides, and also review data in support of inhibition by PI(4,5)P 2 , including recent articles that addressed several aspects of this controversy [65, 84, 105, 114]. In addition, I will also discuss implications of the recent side-chain resolution structures of TRPV1 [9, 57], and show examples on other TRP channels where similar dual effects of PI(4,5)P 2 have been reported.…”

Molecular sensors and modulators of thermoreception

“…70,71 Different approaches used for manipulating the cellular PIP 2 level may underlie the difference, with some including PIP 2 into the whole-cell recording pipette, 65,67 and some applying PIP 2 directly to an inside-out excised patch, 63,68,69 whereas others reconstituting PIP 2 and purified TRPV1 in an artificial liposome or into planar lipid bilayers. 61,64 It should be noted that most of these studies are conducted in expression or reconstitution system, which may also contribute to variable conclusions. A missing study is to determine the role of PIP 2 in native sensory neurons.…”

“…However, there is a continuing controversy regarding the exact role of PIP 2 in TRPV1 activation, with some supporting an inhibiting role, 60,61 and some advocating an stimulating effect, [62][63][64][65][66][67][68][69] whereas others favoring both activating and inhibiting roles depending on certain conditions. 70,71 Different approaches used for manipulating the cellular PIP 2 level may underlie the difference, with some including PIP 2 into the whole-cell recording pipette, 65,67 and some applying PIP 2 directly to an inside-out excised patch, 63,68,69 whereas others reconstituting PIP 2 and purified TRPV1 in an artificial liposome or into planar lipid bilayers.…”