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

Research output: Contribution to journalArticle

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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

Fingerprint

PC12 Cells
Depolarization
Bradykinin
Mercury
mercury
calcium
Adenosine Triphosphate
Phosphatidylinositol Phosphates
Thapsigargin
Clamping devices
Nerve Growth Factor
Cell death
cells
Nifedipine
Verapamil
Caffeine
Cell Differentiation
bradykinin
Cell Death
Electric potential

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.

Modifications of Ca2+ signaling by inorganic mercury in PC12 cells. / Rossi, Anna D.; Labsson, Olof; Manzo, Luigi; Orrenius, Sten; Vahter, Marie; Berggren, Per Olof; Nicotera, Pierluigi.

In: FASEB Journal, Vol. 7, No. 15, 01.12.1993, p. 1507-1514.

Research output: Contribution to journalArticle

Rossi, AD, Labsson, O, Manzo, L, Orrenius, S, Vahter, M, Berggren, PO & Nicotera, P 1993, 'Modifications of Ca2+ signaling by inorganic mercury in PC12 cells', FASEB Journal, vol. 7, no. 15, pp. 1507-1514.
Rossi AD, Labsson O, Manzo L, Orrenius S, Vahter M, Berggren PO et al. Modifications of Ca2+ signaling by inorganic mercury in PC12 cells. FASEB Journal. 1993 Dec 1;7(15):1507-1514.
Rossi, Anna D. ; Labsson, Olof ; Manzo, Luigi ; Orrenius, Sten ; Vahter, Marie ; Berggren, Per Olof ; Nicotera, Pierluigi. / Modifications of Ca2+ signaling by inorganic mercury in PC12 cells. In: FASEB Journal. 1993 ; Vol. 7, No. 15. pp. 1507-1514.
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