P2X4 receptor re-sensitization depends on a protonation/deprotonation cycle mediated by receptor internalization and recycling

The Journal of Physiology
Giorgio FoisManfred Frick

Abstract

Re-sensitization of P2X4 receptors depends on a protonation/de-protonation cycle Protonation and de-protonation of the receptors is achieved by internalization and recycling of P2X4 receptors via acidic compartments Protonation and de-protonation occurs at critical histidine residues within the extracellular loop of P2X4 receptors Re-sensitization is blocked in the presence of the receptor agonist ATP ABSTRACT: P2X4 receptors are members of the P2X receptor family of cation-permeable, ligand-gated ion channels that open in response to the binding of extracellular ATP. P2X4 receptors are implicated in a variety of biological processes, including cardiac function, cell death, pain sensation and immune responses. These physiological functions depend on receptor activation on the cell surface. Receptor activation is followed by receptor desensitization and deactivation upon removal of ATP. Subsequent re-sensitization is required to return the receptor into its resting state. Desensitization and re-sensitization are therefore crucial determinants of P2X receptor signal transduction and responsiveness to ATP. However, the molecular mechanisms controlling desensitization and re-sensitization are not fully understood. In the present st...Continue Reading

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Citations

Oct 26, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Veronika E WinkelmannManfred Frick
Aug 7, 2020·International Journal of Molecular Sciences·Alejandro MontillaMaria Domercq
Jul 18, 2020·International Journal of Molecular Sciences·Eva WirschingManfred Frick
Nov 15, 2020·International Journal of Molecular Sciences·Mira TrangFritz Markwardt
Apr 27, 2021·Frontiers in Immunology·Jean M KanellopoulosDavid M Ojcius

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