Initiation of hyperpermeability in energy-depleted coronary endothelial monolayers.
How the initiation of energy depletion affects macromolecule permeability of a barrier of coronary endothelial cells was investigated. Cultured monolayers of adult rat coronary endothelial cells were exposed to 5 mM KCN and 5 mM 2-deoxy-D-glucose (2-DG). Transendothelial flux of albumin, cellular ATP content, and cytosolic Ca2+ concentration were monitored. Within the first minute, a merely partial loss (28%) of ATP reserves provoked a distinct increase (41%) in albumin flux. Rise of permeability was dependent on Ca2+ release from a thapsigargin- and ATP-sensitive endogenous store, and hyperpermeability was greatly attenuated when energy depletion was extremely rapid, as under sequential addition of 20 mM 2-DG and 5 mM KCN. Attenuation of hyperpermeability could also be achieved by use of 5-20 mM 2,3-butanedione monoxime, an inhibitor of actin-myosin interaction. This finding, together with dependence on Ca2+ and availability of residual energy, indicates that the rapid initiation of hyperpermeability is caused by a contractile mechanism.
Noll
T
T
Physiologisches Institut I, Heinrich-Heine-Universität, Düsseldorf, Germany.
Muhs
A
A
Besselmann
M
M
Watanabe
H
H
Piper
H M
HM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004734:Energy Metabolism; D008297:Male; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism
D012709:Serum Albumin; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D011190:Potassium Cyanide; D002118:Calcium