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

C A Glass, T M Pocock, F E Curry, D O Bates

Microvascular Research Laboratories, Department of Physiology, School of Veterinary Sciences, Southwell Street, University of Bristol, Bristol BS2 8EJ, UK.

The Journal of physiology 2005 May 1

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Vascular permeability is assumed to be regulated by the cytosolic Ca(2+) concentration ([Ca(2+)](c)) of the endothelial cells. When permeability is increased, however, the maximum [Ca(2+)](c) 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+)](c) (d[Ca(2+)](c)/dt) may more closely approximate the time course of the permeability increase. Hydraulic conductivity (L(p)) and endothelial [Ca(2+)](c) were measured in single perfused frog mesenteric microvessels in vivo. The relationships between the time courses of the increased L(p), [Ca(2+)](c) and d[Ca(2+)](c)/dt were examined. L(p) peaked significantly earlier than [Ca(2+)](c) 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+)](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[Ca(2+)](c)/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 d[Ca(2+)](c)/dt (0.30 +/- 0.1 min) both peaked significantly before the [Ca(2+)](c) (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+)](c) rather than the global [Ca(2+)].

Citation

C A Glass, T M Pocock, F E Curry, D O Bates. Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+ concentration in the regulation of vascular permeability in Rana in vivo. The Journal of physiology. 2005 May 1;564(Pt 3):817-27