Cytosolic Ca super(2+) concentration and rate of increase of the cytosolic Ca super(2+) concentration in the regulation of vascular permeability in Rana in vivo

Vascular permeability is assumed to be regulated by the cytosolic Ca super(2+) concentration ([Ca super(2+)] sub(c)) of the endothelial cells. When permeability is increased, however, the maximum [Ca super(2+)] sub(c) appears to occur after the maximum permeability increase, suggesting that Ca super(2+)-dependent mechanisms other than the absolute Ca super(2+) concentration may regulate permeability. Here we investigate whether the rate of increase of the [Ca super(2+)] sub(c) (d[Ca super(2+)] sub(c)/dt) may more closely approximate the time course of the permeability increase. Hydraulic conductivity (L sub(p)) and endothelial [Ca super(2+)] sub(c) were measured in single perfused frog mesenteric microvessels in vivo. The relationships between the time courses of the increased L sub(p), [Ca super(2+)] sub(c) and d[Ca super(2+)] sub(c)/dt were examined. L sub(p) peaked significantly earlier than [Ca super(2+)] sub(c) in all drug treatments examined (Ca super(2+) store release, store-mediated Ca super(2+) influx, and store-independent Ca super(2+) influx). When L sub(p) was increased in a store-dependent manner the time taken for L sub(p) to peak (3.6 plus or minus 0.9 min during store release, 1.2 plus or minus 0.3 min during store-mediated Ca super(2+) influx) was significantly less than the time taken for [Ca super(2+)] sub(c) to peak (9.2 plus or minus 2.8 min during store release, 2.1 plus or minus 0.7 min during store-mediated influx), but very similar to that for the peak d[Ca super(2+)] sub(c)/dt to occur (4.3 plus or minus 2.0 min during store release, 1.1 plus or minus 0.5 min during Ca super(2+) influx). Additionally, when the increase was independent of intracellular Ca super(2+) stores, L sub(p) (0.38 plus or minus 0.03 min) and d[Ca super(2+)] sub(c)/dt (0.30 plus or minus 0.1 min) both peaked significantly before the [Ca super(2+)] sub(c) (1.05 plus or minus 0.31 min). These data suggest that the regulation of vascular permeability by endothelial cell Ca super(2+) may be regulated by the rate of change of the [Ca super(2+)] sub(c) rather than the global [Ca super(2+)].