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Etude moléculaire de la dilatation des récepteurs P2X

Abstract : P2X receptors are nonselective cation channels, permeable to Na +, K + and Ca2 + ions. Their activation by ATP, for membrane potentials close to the resting potential of the cells, induces an influx of cations leading to membrane depolarization. P2X receptors, derived from the oligomerization of three identical (homotrimeric) or heterologous (heterotrimeric) subunits, all possess a transmembrane hydrophobic domain and an extracellular hydrophilic and glycosylated domain. P2X receptors involved in many physiological roles, and have a high tissue distribution. Moreover, since twenty years, a particular conductance of the canal has been discovered allowing the passage of large molecules; which named “dilated state or dilatation of the pore”, this conductance state was considered as a slow process dissociating from the state of conductance which allows the passage of Na+. Our several approach allowed us to understand the mechanism of dilation. However, following our results in electrophysiology, we showed that receptors were immediately dilated in a millisecond time scale. Our results with our photoisomerizable molecules confirmed that dilation was a rapid process. But above all, it solves the molecular mechanism of the dilated state. Indeed under the effect of light, two movements could be observed. We determined that a polyamine, spermidine, could pass through the canal, which had never been demonstrated before. We believe that these results open new physiological perspectives in P2X signaling.
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Mahboubi Harkat. Etude moléculaire de la dilatation des récepteurs P2X. Neurobiologie. Université de Strasbourg, 2017. Français. ⟨NNT : 2017STRAJ023⟩. ⟨tel-02947900⟩

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