bFGF activates endothelial Ca2+-activated K+ channels involving G-proteins and tyrosine kinases

• Published in: Vascular pharmacology Vol. 41; no. 6; pp. 181 - 186
• Main Authors: Kuhlmann, Christoph Rüdiger Wolfram, Wu, Yongjian, Li, Fang, Münz, Benedikt Manuel, Tillmanns, Harald, Waldecker, Bernd, Wiecha, Johannes
• Format: Journal Article
• Language: English
• Published: United States 01.07.2004
• Subjects: Cell Proliferation; Cells, Cultured; Coronary Vessels - cytology; Coronary Vessels - enzymology; Endothelial Cells - enzymology; Female; Fibroblast Growth Factor 2 - metabolism; GTP-Binding Proteins - metabolism; Humans; Membrane Potentials - physiology; Middle Aged; Patch-Clamp Techniques; Potassium Channels, Calcium-Activated - metabolism; Protein-Tyrosine Kinases - metabolism; Signal Transduction - physiology
• ISSN: 1537-1891
• DOI: 10.1016/j.vph.2004.10.003

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.