Basic fibroblast growth factor-induced endothelial proliferation and NO synthesis involves inward rectifier K+ current.
OBJECTIVE
Inward rectifier K+ currents (K(ir)) determine the resting membrane potential and thereby modulate essential Ca2+-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.


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 micromol/L). Perfusion with bFGF (50 ng/mL) caused a significant increase of K(ir), which was blocked by 100 micromol/L barium (n=18, P<0.01). The bFGF-induced HUVEC proliferation was significantly inhibited when using 50 to 100 micromol/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.
Scharbrodt
Wolfram
W
Department of Cardiology and Angiology, Justus-Liebig-University of Giessen, Germany.
Kuhlmann
Christoph Rüdiger Wolfram
CR
Wu
Yongijan
Y
Schaefer
Christian Alexander
CA
Most
Astrid Kerstin
AK
Backenköhler
Ulrich
U
Neumann
Thomas
T
Tillmanns
Harald
H
Waldecker
Bernd
B
Erdogan
Ali
A
Wiecha
Johannes
J
D001464:Barium / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*
D024661:Potassium Channels, Inwardly Rectifying; D016222:Fibroblast Growth Factor 2; D001464:Barium; D009569:Nitric Oxide; D006152:Cyclic GMP; D011188:Potassium; D002118:Calcium