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The heterogeneous calcium concentration in cells is a crucial factor in determining cell function. In this study, the authors investigated the effects of spontaneous fluctuations in intracellular calcium concentration ([Ca(2+)](i)) on endothelial cell adhesion, activation, and morphology. Spontaneous fluctuations in [Ca(2+)](i) (Ca(2+) spiking) were observed in cultured human umbilical vein endothelial cells (HUVECs). In monolayers, sequential Ca(2+) spiking occurred periodically and showed a clear diurnal rhythm (12 to 6 h). Variation in the average Ca(2+) spiking frequency was clearly associated with the expression of intracellular adhesion molecule (ICAM)-1. Adhesion to and migration over collagen and fibronectin of HUVECs were significantly enhanced in cells with high Ca(2+) spiking frequency. L-type calcium channel blockers (nifedipine, 10 nM) and Gd(3+) (30 microM) significantly decreased Ca(2+) spiking frequency. The Ca(2+) spiking frequency was also decreased by treatment with the calcium channel agonist BAYK8644. Prolonged Ca(2+) spiking activity enhanced ICAM-1 expression and enhanced PMN binding to HUVECs. As assessed by laser scanning confocal microscopy, adhesion molecules of HUVECs were translocated to the cell surface following Ca(2+) spiking activity, and ICAM-1 was redistributed from the cytoplasm to the cell surface. In

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