CYTOSOLIC CA2- INJURY TO RAT-KIDNEY PROXIMAL TUBULE EPITHELIAL-CELLS(ELEVATION AND CALPAIN INHIBITORS IN HGCL2 )

This study assessed HgCl2 injury to proximal tubule epithelial cells a s it relates to the concentration of ionized cytosolic Ca2+ ([Ca2+](i) ) elevation and activation of calpains. Experiments in high and low ex tracellular Ca2+ concentration ([Ca2+](e)) were performed using the ca lpain inhibitors antipain and leupeptin, and also trypsin inhibitor, m ethylamine, chloroquine, and ryanodine. Cell killing was time/dose dep endent and greater with high [Ca2+](e). After 30 min treatment with 25 mu M HgCl2, 19% of cells in low [Ca2+](e) were dead while 72% died in high [Ca2+](e). Morphologic changes such as cytoplasmic blebbing were also greater in high [Ca2+](e). Antipain and leupeptin diminished tox icity. Leupeptin did not block Ca2+ entry into cells. Results show tha t HgCl2 toxicity is correlated with increased [Ca2+](i), and that calp ains may mediate the resultant pathological changes.