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 wit h increases in permeability are located in the intercellular clefts or are openings passing through the endothelial cells. 2. Hydraulic perm eability (L(p)) was estimated in frog mesenteric capillaries and singl e rat venules using a microperfusion-micro-occlusion technique before and during perfusion with solutions containing the ionophore A23187 at a concentration of 10 mu M. When L(p) was seen to have increased, the tissues mere fixed in situ with 2.5% glutaraldehyde. 3. The increases in L(p) varied considerably from vessel to vessel. In six frog vessel s L(p) increased from 2.6 +/- 0.9 x 10(-7) to 266 +/- 159 x 10(-7) cm s(-1) cmH(2)O(-1) and in three rat venules L(p) rose from 0.94 +/- 0.0 9 x 10(-7) to 16.4 +/- 4.9 x 10(-7) cm s(-1) cmH(2)O(-1) (means +/- S. E.M.). 4. Forty openings or gaps were completely reconstructed from el ectron micrographs of serial ultrathin sections of the six frog vessel s. Thirty-nine of these gaps passed through the endothelial cells and did not communicate with the intercellular clefts; one was intercellul ar. Similarly, fifteen out of sixteen gaps reconstructed from electron micrographs of the rat venules were transcellular and clearly separat ed from the intercellular clefts. 5. The increased L(p) and associated ultrastructural changes induced by A23187 were reversed by perfusion with ionophore-free solutions.