Tonic Calcium-Activated Chloride Current Sustained by ATP Release and Highly Desensitizing Human P2X1 Receptors

Agenor Limon-Ruiz, Garo Hagopian, Jorge M. Reyes-Ruiz, Ricardo Miledi

Research output: Contribution to journalArticle

Abstract

Extracellular 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.

Original languageEnglish (US)
JournalNeuroscience
DOIs
StatePublished - Jan 1 2019

Fingerprint

Purinergic P2X1 Receptors
Calcium Chloride
Adenosine Triphosphate
Oocytes
Xenopus
Blood Vessels
Exocytosis
Vascular Smooth Muscle
Human Activities
Smooth Muscle Myocytes
Retina
Ligands

Keywords

  • ATP release
  • purinergic signaling
  • tonic activity
  • vascular tone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Tonic Calcium-Activated Chloride Current Sustained by ATP Release and Highly Desensitizing Human P2X1 Receptors. / Limon-Ruiz, Agenor; Hagopian, Garo; Reyes-Ruiz, Jorge M.; Miledi, Ricardo.

In: Neuroscience, 01.01.2019.

Research output: Contribution to journalArticle

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