Basic Fibroblast Growth Factor–Induced Endothelial Proliferation and NO Synthesis Involves Inward Rectifier K + Current

Abstract

Objectives— Inward rectifier K + currents (K ir ) determine the resting membrane potential and thereby modulate essential Ca 2+ -dependent pathways, like cell growth and synthesis of vasoactive agents in endothelial cells. Basic fibroblast growth factor (bFGF) acts as a vasodilatator and angiogenic factor. Therefore, we investigated the effect of bFGF on K ir and assessed the role in proliferation and nitric oxide (NO) formation of endothelial cells. Methods and Results— Using the patch-clamp technique, we found characteristic K ir in human umbilical cord vein endothelial cells (HUVEC), which were dose-dependently blocked by barium (10 to 100 μmol/L). Perfusion with bFGF (50 ng/mL) caused a significant increase of K ir , which was blocked by 100 μmol/L barium (n=18, P <0.01). The bFGF-induced HUVEC proliferation was significantly inhibited when using 50 to 100 μmol/L barium (n=6; P <0.01). NO production was examined using a cGMP radioimmunoassay. bFGF caused a significant increase of cGMP levels (n=10; P <0.05), which were blocked by barium. Conclusions— Modulation of K ir plays an important role in bFGF-mediated endothelial cell growth and NO formation.