Pathways through the intercellular clefts of frog mesenteric capillaries

Area of Science:

• Cell Biology
• Physiology
• Microcirculation Research

Background:

• Understanding endothelial intercellular clefts is crucial for comprehending microvascular permeability.
• The precise structural basis for hydraulic permeability (Lp) in capillaries remains an area of active investigation.

Purpose of the Study:

• To elucidate the three-dimensional ultrastructure of endothelial intercellular clefts in frog mesenteric capillaries.
• To correlate capillary ultrastructure with measured hydraulic permeability (Lp) and the passage of extracellular tracers.

Main Methods:

• Determined hydraulic permeability (Lp) of frog mesenteric capillaries perfused with Ringer solution and albumin.
• Utilized lanthanum nitrate as an electron-dense tracer to identify open pathways in intercellular clefts.
• Employed serial section electron microscopy to reconstruct the three-dimensional ultrastructure of clefts.

Main Results:

• Capillary intercellular clefts exhibit continuous narrow regions interspersed with occasional wider discontinuities.
• Lanthanum tracer filled clefts up to tight junctions, with occasional complete passage through discontinuities.
• The outer leaflets of adjacent endothelial cells at tight junctions were separated by a small gap (approx. 2.3 nm).

Conclusions:

• The structural features of intercellular clefts, including narrow regions and specific discontinuities, dictate capillary hydraulic permeability.
• Lanthanum tracer successfully mapped solute pathways, confirming the role of cleft discontinuities in permeability.
• The findings provide detailed ultrastructural insights into the mechanisms governing microvascular exchange.