Basic fibroblast growth factor-induced endothelial proliferation and NO synthesis involves inward rectifier K+ current

Abstract

Objectives-Inward rectifier K+ currents (Kir) 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 Kir 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 Kir 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 Kir, 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.