Phosphoinositide regulation of TRPV1 revisited

Pflügers Archiv : European journal of physiology
Tibor Rohacs

Abstract

The heat- and capsaicin-sensitive transient receptor potential vanilloid 1 ion channel (TRPV1) is regulated by plasma membrane phosphoinositides. The effects of these lipids on this channel have been controversial. Recent articles re-ignited the debate and also offered resolution to place some of the data in a coherent picture. This review summarizes the literature on this topic and provides a detailed and critical discussion on the experimental evidence for the various effects of phosphatidylinositol 4,5-bisphosphayte [PI(4,5)P2 or PIP2] on TRPV1. We conclude that PI(4,5)P2 and potentially its precursor PI(4)P are positive cofactors for TRPV1, acting via direct interaction with the channel, and their depletion by Ca(2+)-induced activation of phospholipase Cδ isoforms (PLCδ) limits channel activity during capsaicin-induced desensitization. Other negatively charged lipids at higher concentrations can also support channel activity, which may explain some controversies in the literature. PI(4,5)P2 also partially inhibits channel activity in some experimental settings, and relief from this inhibition upon PLCβ activation may contribute to sensitization. The negative effect of PI(4,5)P2 is more controversial and its mechanism is les...Continue Reading

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Citations

Feb 18, 2016·Advances in Pharmacological Sciences·Gregory Smutzer, Roni K Devassy
Jan 5, 2016·Advances in Biological Regulation·Tibor Rohacs
Jul 1, 2015·The Journal of General Physiology·Doreen BadhekaTibor Rohacs
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Apr 12, 2016·The Journal of Physiology·Yevgen YudinTibor Rohacs
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Apr 30, 2020·The Journal of Biological Chemistry·Luyu LiuTibor Rohacs
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May 10, 2021·Bioorganic & Medicinal Chemistry·Alex G Batrouni, Jeremy M Baskin

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