HgCl2-induced changes in cytosolic Ca2+ of cultured rabbit renal tubular cells.
Fura 2 was used to measure changes in cytosolic [Ca2+] ([Ca2+]i) in cultured rabbit kidney proximal tubule cells exposed to HgCl2. Treatment with 2.5-10 microM HgCl2 resulted in an extracellular [Ca2+] ([Ca2+]e)-independent 2- to 12-fold increase in [Ca2+]i above resting levels of about 100 nM. Treatment with 25-100 microM HgCl2 caused a rapid [Ca2+]e-independent 10- to 12-fold increase in [Ca2+]i within 1 min followed by a recovery to about 2-fold steady state by 3 min. With 25-100 microM HgCl2, both magnitude and rate of Ca2+ increase were similar, but recovery was greater with increasing doses. A slower, secondary increase in [Ca2+]i followed which varied with HgCl2 concentration and required [Ca2+]e. The first increase in [Ca2+]i represents release from intracellular pools. Calcium channel blockers, calmodulin inhibitors, and mitochondrial inhibitors do not alter the patterns of [Ca2+]i changes due to HgCl2. The recovery response with higher HgCl2 concentrations appears to be triggered by Hg2+ and not by the increased [Ca2+]i. Sulfhydryl modifiers N-ethylmaleimide, PCMB and PCMBS produced [Ca2+]e-independent [Ca2+]i increases similar to those induced by low HgCl2 concentrations. Cell killing with HgCl2 was about 50% greater with normal [Ca2+]e than with low [Ca2+]e, suggesting that [Ca2+]e influx is important in accelerating injury leading to cell death.
Smith
M W
MW
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
Ambudkar
I S
IS
Phelps
P C
PC
Regec
A L
AL
Trump
B F
BF
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents; D003600:Cytosol / Q000378:metabolism; D016257:Fura-2; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008627:Mercuric Chloride / Q000494:pharmacology*; D008854:Microscopy, Electron; D011817:Rabbits
D001572:Benzofurans; D002614:Chelating Agents; D008627:Mercuric Chloride; D002118:Calcium; D016257:Fura-2