Transcellular gaps in microvascular walls of frog and rat when permeability is increased by perfusion with the ionophore A23187.

1. The experiments described in this paper aimed to determine whether the gaps which develop in microvascular endothelium in association with increases in permeability are located in the intercellular clefts or are openings passing through the endothelial cells. 2. Hydraulic permeability (Lp) was estimated in frog mesenteric capillaries and single rat venules using a microperfusion-micro-occlusion technique before and during perfusion with solutions containing the ionophore A23187 at a concentration of 10 microM. When Lp was seen to have increased, the tissues were fixed in situ with 2.5% glutaraldehyde. 3. The increases in Lp varied considerably from vessel to vessel. In six frog vessels Lp increased from 2.6 +/- 0.9 x 10(-7) to 266 +/- 159 x 10(-7) cm s-1 cmH2O-1 and in three rat venules Lp rose from 0.94 +/- 0.09 x 10(-7) to 16.4 +/- 4.9 x 10(-7) cm s-1 cmH2O-1 (means +/- S.E.M.). 4. Forty openings or gaps were completely reconstructed from electron micrographs of serial ultrathin sections of the six frog vessels. Thirty-nine of these gaps passed through the endothelial cells and did not communicate with the intercellular clefts; one was intercellular. Similarly, fifteen out of sixteen gaps reconstructed from electron micrographs of the rat venules were transcellular and clearly separated from the intercellular clefts. 5. The increased Lp and associated ultrastructural changes induced by A23187 were reversed by perfusion with ionophore-free solutions.