Modifications of Ca2+ signaling by inorganic mercury in PC12 cells.
The effects of different levels of inorganic mercury (Hg2+) on depolarization- or agonist-stimulated Ca2+ signals were studied in PC12 cells. Exposure to 50-300 nM Hg2+ did not alter the resting cytosolic free Ca2+ concentration ([Ca2+]i), but enhanced the Ca2+ response to KCL-induced depolarization. Patch-clamp experiments revealed that these Hg2+ concentrations increased the voltage-dependent Ca2+ current through L-type channels. Also, Hg2+ treatment amplified the intracellular [Ca2+]i transients elicited by extracellular ATP. In contrast, the Ca2+ increase stimulated by bradykinin was unaffected. At slightly higher concentrations (1 to 2 microM), Hg2+ caused a sustained rise of the resting [Ca2+]i. This increase did not occur in Ca(2+)-free medium and was prevented by pretreatment with NiCl2 or with the L-type Ca2+ channel blockers, verapamil and nifedipine. Hg2+ did not mobilize Ca2+ from intracellular stores sensitive to thapsigargin, 2,5-di-(tert-butyl)-benzohydroquinone, or caffeine. At 2 microM, Hg2+ inhibited the [Ca2+]i transients elicited by bradykinin, ATP, or KCl-induced depolarization. The loss of the intracellular Ca2+ response to bradykinin was independent from the Ca2+ overload elicit by Hg2+; instead, it was associated with inhibition of polyphosphoinositide generation. Exposure to the lower Hg2+ concentrations (0.3-0.5 microM) greatly potentiated NGF-induced PC12 cell differentiation. Conversely, treatment with 2 microM Hg2+ caused cell death. Our results show that inorganic mercury has selective and different effects on Ca2+ signaling in PC12 cells depending on the concentration, within a narrow range.
Rossi
A D
AD
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Larsson
O
O
Manzo
L
L
Orrenius
S
S
Vahter
M
M
Berggren
P O
PO
Nicotera
P
P
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D008564:Membrane Potentials; D008628:Mercury / Q000494:pharmacology*; D016716:PC12 Cells; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D015220:Calcium Channels; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D008628:Mercury; D002118:Calcium