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.
Hoyer
J
J
Department of Internal Medicine, University Hospital Benjamin Franklin, Free University Berlin, Germany.
Köhler
R
R
Distler
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005682:Gadolinium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018999:Charybdotoxin; D005682:Gadolinium; D010738:Type C Phospholipases; D002118:Calcium