Modifications of Ca2+ signaling by inorganic mercury in PC12 cells

Anna D. Rossi, Olof Labsson, Luigi Manzo, Sten Orrenius, Marie Vahter, Per Olof Berggren, Pierluigi Nicotera

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59 Scopus citations

Abstract

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 μM), Hg2+ caused a sustained rise of the resting [Ca2+]i. This increase did not occur in Ca2+-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 μM, 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 elicited by Hg2+; instead, it was associated with inhibition of polyphosphoinositide generation. Exposure to the lower Hg2+ concentrations (0.3-0.5 μM greatly potentiated NGF-induced PC12 cell differentiation. Conversely, treatment with 2 μM 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.

Original languageEnglish
Pages (from-to)1507-1514
Number of pages8
JournalFASEB Journal
Volume7
Issue number15
StatePublished - Dec 1 1993
Externally publishedYes

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Keywords

  • Ca channels
  • Inositol polyphosphates
  • Signal transduclion

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Rossi, A. D., Labsson, O., Manzo, L., Orrenius, S., Vahter, M., Berggren, P. O., & Nicotera, P. (1993). Modifications of Ca2+ signaling by inorganic mercury in PC12 cells. FASEB Journal, 7(15), 1507-1514.