Intracellular cross talk and physical interaction between two classes of neurotransmitter-gated channels

Fast chemical communications in the nervous system are mediated by several classes of receptor channels believed to be independent functionally and physically. We show here that concurrent activation of P2X 2 ATP-gated channels and 5-HT 3 serotonin-gated channels leads to functional interaction and nonadditive currents (47-73% of the predicted sum) in mammalian myenteric neurons as well as in Xenopus oocytes or transfected human embryonic kidney (HEK) 293 cell heterologous systems. We also show that these two cation channels coimmunoprecipitate constitutively and are associated in clusters. In heterologous systems, the inhibitory cross talk between P2X 2 and 5-HT 3 receptors is disrupted when the intracellular C-terminal domain of the P2X 2 receptor subunit is deleted and when minigenes coding for P2X 2 or 5-HT 3 A receptor subunit cytoplasmic domains are overexpressed. Injection of fusion proteins containing the C-terminal domain of P2X 2 receptors in myenteric neurons also disrupts the functional interaction between native P2X 2 and 5-HT 3 receptors. Therefore, activity-dependent intracellular coupling of distinct receptor channels underlies ionotropic cross talks that may significantly contribute to the regulation of neuronal excitability and synaptic plasticity

Heterologous functional interactions of P2X ATP receptors

Part I. In this work we show that P2X3 currents are acutely modulated by the GPCRs mGluR5 and P2Y2, and by the neurotrophin TrkA receptor, expressed in nociceptors, in the recombinant Xenopus oocyte system. The intracellular C-terminal domain of P2X 3 plays an important role in its functional coupling to TrkA. Preliminary studies suggest a role for PKC in the P2X3-TrkA cross-talk, but other routes may also contribute. Part II. Neurogenic and pharmacological stimulation of vascular smooth muscle P2X1 elicits a contractile response that we found was potentiated by serotonin acting through 5HT2A. We also found in Xenopus oocytes that P2X 1 currents in the desensitized state are potentiated by M1 ACh receptors and by phorbol ester stimulation of PKC. Part III. We have shown in Boue-Grabot et al. (2003) that there was an intracellular negative cross-talk and physical interaction between P2X2 and 5HT3A receptors. We also found a functional interaction between P2X2 and GABAA alpha2beta 3 receptor subtypes in HEK293 mammalian cells and in Xenopus oocytes; and we confirmed the findings of Sokolova et al. , (2001) in primary cultures of DRG neurons. (Abstract shortened by UMI.

La schizophrénie : Adhérer à l'espoir

Vidéo disponible sur YouTube à l'adresse : https://www.youtube.com/watch?v=cciXBD72wH8Pour toute question : [email protected] réalisé dans le cadre du cours PHA2415Ce vidéo présente le témoignage d'une personne atteinte de schizophrénie, de l'apparition de ses symptômes jusqu'à son adhésion au traitement pharmacologique et psychosocial. On y voit notamment la stigmatisation dont il était victime, l'impact de la maladie sur son quotidien et ce qui l'a convaincu à adhérer à son traitement.Société québécoise de la schizophréni

Intracellular Cross Talk and Physical Interaction between Two Classes of Neurotransmitter-Gated Channels

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