Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+ concentration in the regulation of vascular permeability in Rana in vivo.

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