bFGF activates endothelial Ca2+-activated K+ channels involving G-proteins and tyrosine kinases.
Activation of Ca2+-activated K+ channels (BK(Ca)) has been shown to be an important step in the basic fibroblast growth factor (bFGF)-induced proliferation of endothelial cells. In this study, we investigate the signaling cascades of BK(Ca) modulation by bFGF. Using the patch-clamp technique, bFGF (50 ng/ml) significantly increased the BK(Ca) open-state probability in cultured endothelial cells derived from human coronary arteries after 6 min (n=26, p<0.01), which lasted up the whole recording time of 60 min. After preincubation with pertussis toxin (100 ng/ml), bFGF superfusion did not cause a significant increase of BK(Ca) activity until 25 min had passed. When genistein was supplemented to the bath solution, a significant activation of BK(Ca) by bFGF was observed during a time interval of 6-20 min (n=17, p<0.01). In contrast, the addition of the inactive analogue daidzein did not change bFGF-induced activation of the BK(Ca). In conclusion, the results of the present study indicate that the early activation of the BK(Ca) by bFGF is mediated by G-protein-dependent mechanisms, whereas the later effect is due to a tyrosine kinase-dependent signaling pathway.
Kuhlmann
Christoph Rüdiger Wolfram
CR
Justus-Liebig-University of Giessen, Department of Cardiology and Angiology, Klinikstrasse 36, 35392 Giessen, Germany. Christoph.R.Kuhlmann@innere.med.uni-giessen.de
Wu
Yongjian
Y
Li
Fang
F
Münz
Benedikt Manuel
BM
Tillmanns
Harald
H
Waldecker
Bernd
B
Wiecha
Johannes
J
D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000201:enzymology; D042783:Endothelial Cells / Q000201:enzymology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D024681:Potassium Channels, Calcium-Activated; D016222:Fibroblast Growth Factor 2; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins