Mechanosensitive Ca2+ oscillations and STOC activation in endothelial cells

Area of Science:

• Endothelial cell biology
• Cardiovascular physiology
• Mechanotransduction

Background:

• Ion channel activation and intracellular calcium ([Ca2+]i) increase are crucial for endothelial responses to hemodynamic forces.
• Endothelial cells regulate vascular tone through complex signaling pathways.
• Understanding these pathways is key to cardiovascular health.

Purpose of the Study:

• To investigate the role of shear stress in activating ion channels and intracellular calcium signaling in endothelial cells.
• To elucidate the signaling mechanisms underlying endothelial responses to mechanical forces.
• To identify novel pathways in endothelial mechanotransduction.

Main Methods:

• Utilized a parallel flow chamber to apply shear stress to bovine aortic endothelial cells.
• Measured hyperpolarizing K+ currents and intracellular Ca2+ oscillations.
• Investigated the dependence of these responses on extracellular calcium, calcium stores, and specific channel modulators (Gd3+, BHQ, ryanodine, heparin).

Main Results:

• Shear stress activated spontaneous transient outward currents (STOCs), which are hyperpolarizing K+ currents.
• STOCs occurred simultaneously with oscillating increases in [Ca2+]i.
• STOC activation was dependent on Ca2+ influx and release from ryanodine-sensitive stores, but not heparin-sensitive stores.
• These findings were replicated in intact endothelium.

Conclusions:

• Endothelial responses to shear stress involve coordinated activation of STOCs and oscillating [Ca2+]i.
• This process is mediated by calcium influx-induced calcium release from ryanodine-sensitive intracellular stores.
• A novel signaling pathway in endothelial mechanotransduction has been identified.