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Non‐acidic activation of pain‐related Acid‐Sensing Ion Channel 3 by lipids
Author(s) -
Marra Sébastien,
FerruClément Romain,
Breuil Véronique,
Delaunay Anne,
Christin Marine,
Friend Valérie,
Sebille Stéphane,
Cognard Christian,
Ferreira Thierry,
Roux Christian,
EullerZiegler Liana,
Noel Jacques,
Lingueglia Eric,
Deval Emmanuel
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201592335
Subject(s) - nice , art history , humanities , art , computer science , programming language
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.