Thapsigargin increases cellular free calcium and intracellular sodium concentrations in cultured rat glomerular...

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 Ca(2+)-free medium containing 1 x 10(-4) M EGTA. An increase in [Ca2+]i by thapsigargin was not altered by 1 x 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 Ca(2+)-free medium completely blocked the increase in [Na+]i by thapsigargin. These results indicate that thapsigargin increases [Ca2+]i by blocking endoplasmic Ca(2+)-ATPase and enhancing Ca2+ entry, and that the increased Ca2+ influx is triggering an increase in [Na+]i stimulated by thapsigargin per se in glomerular mesangial cells.