Mechanosensitive Ca2+ oscillations and STOC activation in endothelial cells.

Activation of ion channels and the increase in intracellular Ca2+ concentration [Ca2+]i play a key role in endothelial responses to hemodynamic forces and subsequent vasoregulation. In bovine aortic endothelial cells subjected to shear stress in a parallel flow chamber, we demonstrate shear stress activation of hyperpolarizing K+ currents that occur simultaneously with oscillating increases of [Ca2+]i. Oscillating K+ currents, also known as spontaneous transient outward currents (STOC), were regulated in frequency and amplitude by the rate of shear stress in a range from 5 to 18 dyn/cm2. Activation of STOC depended on Ca2+ influx; current depended on the extracellular Ca2+ concentration and was blocked by 50 microM Gd3+. Emptying of Ca2+ stores by BHQ abolished current responses to shear stress. STOC activation was significantly reduced by cell dialysis with ryanodine (20 microM), but not heparin (200 microg/ml). Shear stress-induced STOC activation was also observed in the intact endothelium. The endothelial response to shear stress involves oscillating [Ca2+]i increase and STOC activation, which depend on Ca2+ influx-induced Ca2+ release from ryanodine-sensitive stores, demonstrating a new signaling pathway in endothelial mechanotransduction.