Promiscuous Activation of Transient Receptor Potential Vanilloid 1 (TRPV1) Channels by Negatively Charged Intracellular Lipids

• DOI: 10.1074/jbc.m113.520288
• Publication Date: 2013-10-25T06:27:17Z
• Authors: Viktor Lukacs; Jan-Michael Rives; Xiaohui Sun; Eleonora Zakharian; Tibor Rohacs
• Keywords: Capsaicin

The regulation of the heat- and capsaicin-activated transient receptor potential vanilloid 1 (TRPV1) channels by phosphoinositides is controversial. Data in cellular systems support dependence TRPV1 activity on phosphoinositides. purified TRPV1, however, was recently shown to be fully functional artificial liposomes absence Here, we show that several other negatively charged phospholipids, including phosphatidylglycerol, can also excised patches at high concentrations. When incorporated into planar lipid bilayers consisting neutral lipids, capsaicin-induced depended phosphatidylinositol 4,5-bisphosphate. We found ran down MgATP reactivated channel. Inhibition 4-kinases or enzymatic removal abolished this effect MgATP, suggesting it activated generating endogenous conclude are positive cofactors for activity. Our data highlight importance specificity ion may reconcile discordant obtained various experimental settings.