Referenced in: none

Automatically associated channels: Slo1

Title: Non-acidic activation of pain-related Acid-Sensing Ion Channel 3 by lipids.

Authors: Sébastien Marra, Romain Ferru-Clément, Véronique Breuil, Anne Delaunay, Marine Christin, Valérie Friend, Stéphane Sebille, Christian Cognard, Thierry Ferreira, Christian Roux, Liana Euller-Ziegler, Jacques Noël, Eric Lingueglia, Emmanuel Deval

Journal, date & volume: EMBO J., 2016 Feb 15 , 35, 414-28

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26772186

Abstract
Extracellular pH variations are seen as the principal endogenous signal that triggers activation of Acid-Sensing Ion Channels (ASICs), which are basically considered as proton sensors, and are involved in various processes associated with tissue acidification. Here, we show that human painful inflammatory exudates, displaying non-acidic pH, induce a slow constitutive activation of human ASIC3 channels. This effect is largely driven by lipids, and we identify lysophosphatidylcholine (LPC) and arachidonic acid (AA) as endogenous activators of ASIC3 in the absence of any extracellular acidification. The combination of LPC and AA evokes robust depolarizing current in DRG neurons at physiological pH 7.4, increases nociceptive C-fiber firing, and induces pain behavior in rats, effects that are all prevented by ASIC3 blockers. Lipid-induced pain is also significantly reduced in ASIC3 knockout mice. These findings open new perspectives on the roles of ASIC3 in the absence of tissue pH variation, as well as on the contribution of those channels to lipid-mediated signaling.