[ATP release pathways in vascular endothelial cells].

Area of Science:

• Cellular Physiology
• Endothelial Cell Biology
• Mechanotransduction

Background:

• Vascular endothelial cells respond to mechanical stress by releasing adenosine triphosphate (ATP).
• Released ATP acts in an auto/paracrine manner to influence neighboring cells, affecting calcium (Ca2+) responses and nitric oxide (NO) production.
• The precise cellular mechanisms and pathways responsible for ATP release, particularly in response to mechanical stimuli, remain largely undefined.

Purpose of the Study:

• To investigate the role of volume-regulated anion channels (VRAC) in mechanosensitive ATP release from vascular endothelial cells.
• To explore the interaction between extracellular ATP and VRAC function in the endothelium.

Main Methods:

• Utilized bovine aortic endothelial cells.
• Assessed ATP release under hypotonic stress conditions.
• Employed VRAC inhibitors to evaluate their effect on ATP release.
• Measured VRAC currents in the presence of extracellular ATP using electrophysiology.

Main Results:

• Inhibitors of volume-regulated anion channels (VRAC) significantly reduced ATP release induced by hypotonic stress in endothelial cells.
• Extracellular ATP demonstrated a voltage-dependent inhibitory effect on VRAC currents, consistent with a permeation-blocker model.
• Basal ATP release was not suppressed by VRAC inhibitors, suggesting the involvement of additional ATP release pathways.

Conclusions:

• Volume-regulated anion channels (VRAC) are a significant pathway for mechanosensitive ATP release in vascular endothelium.
• Extracellular ATP can modulate VRAC activity, indicating a potential feedback mechanism.
• Further research is necessary to fully elucidate the mechanisms and therapeutic implications of ATP release in the endothelium.