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

Abstract

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 (L_p) and endothelial [Ca²⁺]_c were measured in single perfused frog mesenteric microvessels in vivo. The relationships between the time courses of the increased L_p, [Ca²⁺]_c and d[Ca²⁺]_c/dt were examined. L_p peaked significantly earlier than [Ca²⁺]_c in all drug treatments examined (Ca²⁺ store release, store-mediated Ca²⁺ influx, and store-independent Ca²⁺ 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 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, L_p (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⁺].