Next Article in Journal
CA 19-9 Pancreatic Tumor Marker Fluorescence Immunosensing Detection via Immobilized Carbon Quantum Dots Conjugated Gold Nanocomposite
Next Article in Special Issue
Calcium and Nuclear Signaling in Prostate Cancer
Previous Article in Journal
An Overview on the Clinical Development of Tau-Based Therapeutics
Previous Article in Special Issue
Dandelion Root Extract Induces Intracellular Ca2+ Increases in HEK293 Cells
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(4), 1161; doi:10.3390/ijms19041161

Opposing Roles of Calcium and Intracellular ATP on Gating of the Purinergic P2X2 Receptor Channel

1
Section on Cellular Signaling, National Institutes of Child Health and Human Development, NIH, Bethesda, MD 20892, USA
2
Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo 1781421, Chile
3
Laboratory of Developmental Physiology, Department of Physiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4030000, Chile
4
Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, Chile
5
Centro para el Desarrollo de Nanociencias y Nanotecnología (CEDENNA), Santiago 9170022, Chile
Deceased on March 2017.
*
Author to whom correspondence should be addressed.
Received: 6 March 2018 / Revised: 30 March 2018 / Accepted: 3 April 2018 / Published: 11 April 2018
(This article belongs to the Special Issue Calcium Signaling in Human Health and Diseases)
View Full-Text   |   Download PDF [2880 KB, uploaded 13 April 2018]   |  

Abstract

P2X2 receptors (P2X2R) exhibit a slow desensitization during the initial ATP application and a progressive, calcium-dependent increase in rates of desensitization during repetitive stimulation. This pattern is observed in whole-cell recordings from cells expressing recombinant and native P2X2R. However, desensitization is not observed in perforated-patched cells and in two-electrode voltage clamped oocytes. Addition of ATP, but not ATPγS or GTP, in the pipette solution also abolishes progressive desensitization, whereas intracellular injection of apyrase facilitates receptor desensitization. Experiments with injection of alkaline phosphatase or addition of staurosporine and ATP in the intracellular solution suggest a role for a phosphorylation-dephosphorylation in receptor desensitization. Mutation of residues that are potential phosphorylation sites identified a critical role of the S363 residue in the intracellular ATP action. These findings indicate that intracellular calcium and ATP have opposing effects on P2X2R gating: calcium allosterically facilitates receptor desensitization and ATP covalently prevents the action of calcium. Single cell measurements further revealed that intracellular calcium stays elevated after washout in P2X2R-expressing cells and the blockade of mitochondrial sodium/calcium exchanger lowers calcium concentrations during washout periods to basal levels, suggesting a role of mitochondria in this process. Therefore, the metabolic state of the cell can influence P2X2R gating. View Full-Text
Keywords: purinergic receptor channels; desensitization; ATP; calcium; allosteric; covalent purinergic receptor channels; desensitization; ATP; calcium; allosteric; covalent
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Share & Cite This Article

MDPI and ACS Style

Rokic, M.B.; Castro, P.; Leiva-Salcedo, E.; Tomic, M.; Stojilkovic, S.S.; Coddou, C. Opposing Roles of Calcium and Intracellular ATP on Gating of the Purinergic P2X2 Receptor Channel. Int. J. Mol. Sci. 2018, 19, 1161.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top