Mechanosensitive Ca2+ transients in endothelial cells from human umbilical vein.
We have investigated the changes in intracellular calcium concentration ([Ca2+]i) in human endothelial cells induced by mechanical stretch due to osmotic cell swelling. Hypotonic solutions also activate a Cl- conductance that has been described elsewhere and mainly serves to clamp the membrane potential at negative values to provide a driving force for Ca2+ influx. The increase in [Ca2+]i caused by hypotonic solutions is due to release from inositol-1,4,5-trisphosphate-sensitive Ca2+ pools and a subsequent Ca2+ influx, apparently activated by store depletion. These changes in [Ca2+]i are completely abolished if the phospholipase A2 (PLA2) activity is inhibited by either 4-bromophenacyl bromide or cyclosporin A. Arachidonic acid, applied either extracellularly or intracellularly via the patch pipette, mimics the mechanosensitive response even in cells with blocked PLA2. Metabolites of the lipo- and cyclooxygenase pathways can be excluded. Phospholipase C activation and the protein kinase A pathway are not involved in this mechanical response. Although no specific pharmacological tools for probing the role of PLA2 are available, our evidence suggests that mechanosensitivity in endothelial cells may be modulated by arachidonic acid.
Oike
M
M
KU Leuven, Laboratorium voor Fysiologie, Belgium.
Droogmans
G
G
Nilius
B
B
D016718:Arachidonic Acid / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D015398:Signal Transduction; D013314:Stress, Mechanical; D010738:Type C Phospholipases / Q000378:metabolism; D014471:Umbilical Veins
D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D002118:Calcium