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Tonic Calcium-Activated Chloride Current Sustained by ATP Release and Highly Desensitizing Human P2X1 Receptors
Agenor Limon1, Garo Hagopian2, Jorge M Reyes-Ruiz2
1Department 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.
Neuroscience
|July 27, 2019
Summary
Xenopus oocytes release adenosine triphosphate (ATP) constitutively, sustaining tonic activity of human P2X1 receptors and calcium-activated chloride channels. Extracellular calcium amplifies this P2X1 receptor activity, offering potential pharmaceutical targets for vascular tone regulation.
Area of Science:
- Neuroscience
- Molecular Biology
- Physiology
Background:
- Extracellular adenosine triphosphate (ATP) is crucial for maintaining central nervous system vascular tone, particularly in the retina.
- P2X1 receptors, known for high ATP affinity and desensitization, mediate this tonic activity, but the underlying mechanism is unclear.
- Understanding P2X1 receptor function is vital for insights into vascular regulation and potential therapeutic strategies.
Purpose of the Study:
- To investigate the relationship between spontaneous ATP release from Xenopus oocytes and the tonic activity of human P2X1 receptors.
- To explore the role of calcium-activated chloride channels in modulating P2X1 receptor function.
- To elucidate mechanisms regulating vascular tone and identify potential pharmaceutical targets.
Main Methods:
- Expression of human P2X1 (hP2X1) homomeric receptors in Xenopus oocytes.
- Measurement of ATP release from oocytes at rest.
- Assessment of hP2X1 receptor activity and its coupling with Ca2+-activated Cl- channels.
Main Results:
- Xenopus oocytes exhibit constitutive ATP release via vesicular exocytosis, independent of extracellular calcium.
- hP2X1 receptors sustain tonic activity of Ca2+-activated Cl- channels.
- Extracellular calcium significantly amplifies hP2X1 receptor activity through coupling with Ca2+-activated Cl- channels.
Conclusions:
- Spontaneous ATP release from oocytes supports tonic P2X1 receptor activity.
- P2X1 receptors and Ca2+-activated Cl- channels form a functional unit influencing cellular activity.
- Further research into hP2X1 and Ca2+-activated Cl- channels in vascular smooth muscle could reveal novel therapeutic targets for vascular tone regulation.
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