title: 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 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+)].
authors.affiliation: Microvascular Research Laboratories, Department of Physiology, School of Veterinary Sciences, Southwell Street, University of Bristol, Bristol BS2 8EJ, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Glass
authors.forename: T M
authors.initials: TM
authors.lastname: Pocock
authors.forename: F E
authors.initials: FE
authors.lastname: Curry
authors.forename: D O
authors.initials: DO
authors.lastname: Bates
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D011896:Rana temporaria / Q000502:physiology*
chemical_list: D002118:Calcium
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