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Couplage fonctionnel entre un récepteur et un canal ionique: étude du canal KATP et application pour la création de biocapteurs

Julien P. Dupuis 1
1 LPM - Laboratoire des Protéines Membranaires
IBS - UMR 5075 - Institut de biologie structurale
Abstract : ATP-sensitive potassium channels (KATP) play a critical role in pancreatic insulin secretion and participate in the vascular tone control as well as cardiac myocyte and neuron excitability. Formed by the unique association of a membrane receptor of the ABC transporters family, the sulfonylurea receptor SUR, and an inward rectifier potassium channel, Kir6.2, they couple the membrane potential to the cell metabolism. Therefore, they can be considered as a natural example of biosensor.
The unique property of this complex is that SUR adjusts Kir6.2 gating as a function of physiological and pharmacological ligands (nucleotides, synthetic activators and inhibitors). We addressed the question of identifying the molecular elements underlying functional coupling between SUR and Kir6.2. Following a chimerical strategy, we identified an essential C-terminal region of isoform SUR2A which functionally links ligand binding to SUR to Kir6.2 upregulation.
Using our knowledge of the KATP model, we also developed a new type of electrical biosensor, Ion Channel Coupled Receptors (ICCRs), based on the artificial functional coupling of Kir6.2 with G-protein coupled receptors (GPCRs). Using protein engineering, we created two prototypes of ICCRs based on the muscarinic M2 and dopaminergic D2 receptors: agonist or antagonist binding to these receptors leads to real-time electrically measurable channel activations or inhibitions. ICCRs constitute the promising premises of a new generation of cell-free biosensors.
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https://tel.archives-ouvertes.fr/tel-00320387
Contributor : Julien Dupuis <>
Submitted on : Wednesday, September 10, 2008 - 6:08:40 PM
Last modification on : Wednesday, November 4, 2020 - 3:03:17 PM
Long-term archiving on: : Saturday, November 26, 2016 - 1:25:25 AM

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  • HAL Id : tel-00320387, version 1

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Julien P. Dupuis. Couplage fonctionnel entre un récepteur et un canal ionique: étude du canal KATP et application pour la création de biocapteurs. Physiologie [q-bio.TO]. Université Joseph-Fourier - Grenoble I, 2008. Français. ⟨tel-00320387⟩

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