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Régulation des canaux ASIC par les lipides et la température – Conséquences sur les perceptions sensorielles et douloureuses

Abstract : Acid-Sensing Ion channel 3 (ASIC3) is a member of the ASIC family (ASIC1-4), which are excitatory ion channels activated by extracellular acidosis. Proton remains so far the unique endogenous activator of ASIC. ASIC3 channels are expressed in peripheral sensory neurons which innervate skin, muscles, viscera and joints. In rodents, they have been reported to be involved in the detection of different types of pain, including inflammatory pain, postoperative pain and arthritis. During my thesis, I studied the regulation of ASIC3 channels and their involvement in sensory and painful perceptions. The first part of my thesis project allowed the discovery for the first time of new endogenous activators of ASIC3 channels, which differ from protons. I demonstrated that lipids (i.e., lysophosphatidylcholine and arachidonic acid) present in human painful synovial fluids from patient with different joint pathologies, are able to activate ASIC3 channels without any extracellular acidification. These lipids are able to generate an acute painful behavior in rodents mediated, in a large part, by ASIC3. During the second part of my thesis I was interested by the regulation of ASIC3 channels by temperature. I demonstrated that these channels are activated by cold temperature (i.e., 15°C) at physiological pH. These results are reinforced by behavior experiments, showing an implication of ASIC3 in the perception of noxious and innocuous cold.
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Sébastien Marra. Régulation des canaux ASIC par les lipides et la température – Conséquences sur les perceptions sensorielles et douloureuses. Sciences agricoles. Université Côte d'Azur, 2017. Français. ⟨NNT : 2017AZUR4054⟩. ⟨tel-01968053⟩

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