THAPSIGARGIN INCREASES CELLULAR FREE CALCIUM AND INTRACELLULAR SODIUM CONCENTRATIONS IN CULTURED RAT GLOMERULAR MESANGIAL CELLS

We examined whether thapsigargin increases cellular free calcium ([Ca2+](i)) and intracellular sodium concentration ([Na+](i)) in cultured rat glomerular mesangial cells. 1 x 10-6 M Thapsigargin increased [Ca2+](i) to 244.4 from 86.6 nM, an increase sustained at least during the 15 min observation period. Such an increase in [Ca2+](i) was transient in Ca2+-free medium containing 1 x 10-4 M EGTA. An increase in [Ca2+](i) by thapsigargin was not altered by 1 × 10-6 M nicardipine, a L-type Ca2+ channel blocker. Thapsigargin also produced a sustained rise in [Na+](i) in a dose-dependent manner. However, preincubation of cells with Ca2+-free medium completely blocked the increase in [Na+](i) by thapsigargin. These results indicate that thapsigargin increases [Ca2+](i) by blocking endoplasmic Ca2+-ATPase and enhancing Ca2+ entry, and that the increased Ca2+ influx is triggering and increase in [Na+](i) stimulated by thapsigargin per se in glomerular mesangial cells. © 1993 Academic Press, Inc.