• Agenor Limon, Garo Hagopian, Jorge M Reyes-Ruiz, and Ricardo Miledi.
• Department of Neurology, Mitchel Center for Neurodegenerative Diseases, School of Medicine, University of Texas Medical Branch at Galveston, USA; Department of Neurobiology and Behavior, School of Medicine, University of California Irvine, USA. Electronic address: aglimonr@utmb.edu.
• Neuroscience. 2020 Jul 15; 439: 332-341.

AbstractExtracellular adenosine triphosphate (ATP) participates in maintaining the vascular tone in the CNS, particularly in the retina, via the tonic activity of ligand gated activated P2X1 receptors. P2X1 receptors are characterized by their high affinity for ATP and their strong desensitization to concentrations of ATP that are 200-fold lower than their EC50. The mechanism behind P2X1 tonic activity remains unclear. In this study, we expressed human P2X1 (hP2X1) homomeric receptors in Xenopus oocytes to explore the relationship between ATP release from oocytes at rest, hP2X1, and Ca2+-activated Cl- channels. Our results indicate that Xenopus oocytes release ATP at rest via vesicular exocytosis, and this process is a constitutive phenomenon independent of extracellular Ca2+. Our results also indicate that hP2X1 receptors are able to sustain a tonic activity of Ca2+-activated Cl- channels. In the presence of extracellular Ca2+ the activity of hP2X1 receptors is greatly amplified by its coupling with Ca2+-activated Cl- channels. Future studies addressing the relationship between hP2X1 receptors and Ca2+-activated Cl- channels in vascular smooth muscle cells should provide information about additional mechanisms that regulate the vascular tone and their potential as pharmaceutical targets. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.

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