Vascular permeability is assumed to be regulated by the cytosolic Ca2+ concentration ([Ca2+]c) of the endothelial cells. When permeability is increased, however, the maximum [Ca2+]c, appears to occur after the maximum permeability increase, suggesting that Ca2+ -dependent mechanisms other than the absolute Ca2+ concentration may regulate permeability. Here we investigate whether the rate of increase of the [Ca2+]c (d[Ca2+]c/dt) may more closely approximate the time course of the permeability increase. Hydraulic conductivity (Lp) and endothelial [Ca2+]c were measured in single perfused frog mesenteric microvessels in vivo. The relationships between the time courses of the increased Lp, [Ca2+]c and d[Ca2+]c/dt were examined. Lp peaked significantly earlier than [Ca2+]c in all drug treatments examined (Ca2+ store release, store-mediated Ca2+ influx, and store-independent Ca2+ influx). When Lp was increased in a store-dependent manner the time taken for Lp to peak (3.6 ± 0.9 min during store release, 1.2 ± 0.3 min during store-mediated Ca2+ influx) was significantly less than the time taken for [Ca2+]c to peak (9.2 ± 2.8 min during store release, 2.1 ± 0.7 min during store-mediated influx), but very similar to that for the peak d[Ca2+]c/dt to occur (4.3 ± 2.0 min during store release, 1.1 ± 0.5 min during Ca2+ influx). Additionally, when the increase was independent of intracellular Ca2+ stores, Lp (0.38 ± 0.03 min) and d[Ca2+]c/dt (0.30 ± 0.1 min) both peaked significantly before the [Ca2+]c (1.05 ± 0.31 min). These data suggest that the regulation of vascular permeability by endothelial cell Ca2+ may be regulated by the rate of change of the [Ca2+]c rather than the global [Ca2+].
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