MECHANOSENSITIVE CA2-CELLS FROM HUMAN UMBILICAL VEIN( TRANSIENTS IN ENDOTHELIAL)

We have investigated the changes in intracellular calcium concentratio n ([Ca2+]i) in human endothelial cells induced by mechanical stretch d ue to osmotic cell swelling. Hypotonic solutions also activate a Cl- c onductance that has been described elsewhere and mainly serves to clam p the membrane potential at negative values to provide a driving force for Ca2+ influx. The increase in [Ca2+]i caused by hypotonic solution s is due to release from inositol-1,4,5-trisphosphate-sensitive Ca2+ p ools and a subsequent Ca2+ influx, apparently activated by store deple tion. These changes in [Ca2+]i are completely abolished if the phospho lipase A2 (PLA2) activity is inhibited by either 4-bromophenacyl bromi de 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 a nd the protein kinase A pathway are not involved in this mechanical re sponse. Although no specific pharmacological tools for probing the rol e of PLA2 are available, our evidence suggests that mechanosensitivity in endothelial cells may be modulated by arachidonic acid.