Vascular endothelial growth factor-A activates Ca2+ -activated K+ channels in human endothelial cells in culture

The International Journal of Biochemistry & Cell Biology
M FaehlingJ Waltenberger

Abstract

Vascular endothelial growth factor-A (VEGF-A) is an endothelial-cell specific growth factor and leads to an increase in cytosolic free calcium ([Ca2+](i)) in endothelial cells. Ca2+ -activated K+ channels (KCa-channels) have been suggested to facilitate calcium influx by hyperpolarising the cell and thus increasing the electrochemical driving force for calcium influx. The patch-clamp technique was used to investigate the effect of VEGF-A on large conductance KCa-channels. The role of these channels in VEGF-induced proliferation (cell count, [3H]thymidine incorporation) was studied using the specific inhibitor iberiotoxin. VEGF-A strongly stimulated KCa-channel activity and led to a 14.2 +/- 4.8 fold (SEM, n = 12) increase in activity after 8 min of VEGF-A stimulation. The VEGF-A-induced activation occurred in calcium-free solution as well (16.7+/-2.2 fold, SEM, n = 5) whereas carboxyamidotriazole (CAI), an antiangiogenic drug which inhibits both Ca2+ influx and Ca2+ release from intracellular stores, completely blocked VEGF-A-induced KCa channel activation. Specific inhibition of KCa channel activity with iberiotoxin did not inhibit proliferation of endothelial cells induced by VEGF-A and or basic fibroblast growth factor (bFGF...Continue Reading

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Citations

Dec 20, 2005·The Journal of Membrane Biology·L A PardoW Stühmer
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