bFGF activates endothelial Ca 2+-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: Elsevier Inc 2004
• Subjects: Basic fibroblast growth factor; Calcium-activated potassium channel; Daidzein; Genistein; Human coronary artery endothelial cells; Pertussis toxin; Tyrosine kinases; Human coronary artery endothelial cells; Calcium-activated potassium channel; Genistein; Tyrosine kinases; Basic fibroblast growth factor; Daidzein; Pertussis toxin
• ISSN: 1537-1891; 1879-3649
• DOI: 10.1016/j.vph.2004.10.003

Activation of Ca 2+-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.