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

This study assessed HgCl2 injury to proximal tubule epithelial cells as it relates to the concentration of ionized cytosolic Ca2+ ([Ca2+](i)) elevation and activation of calpains. Experiments in high and low extracellular Ca2+ concentration ([Ca2+](e)) were performed using the calpain inhibitors antipain and leupeptin, and also trypsin inhibitor, methylamine, chloroquine, and ryanodine. Cell killing was time/dose dependent 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 toxicity. Leupeptin did not block Ca2+ entry into cells. Results show that HgCl2 toxicity is correlated with increased [Ca2+](i), and that calpains may mediate the resultant pathological changes.