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 language | English |
|---|---|
| Pages (from-to) | 1507-1514 |
| Number of pages | 8 |
| Journal | FASEB Journal |
| Volume | 7 |
| Issue number | 15 |
| State | Published - Dec 1 1993 |
| Externally published | Yes |
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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
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 journal › Article
}
TY - JOUR
T1 - Modifications of Ca2+ signaling by inorganic mercury in PC12 cells
AU - Rossi, Anna D.
AU - Labsson, Olof
AU - Manzo, Luigi
AU - Orrenius, Sten
AU - Vahter, Marie
AU - Berggren, Per Olof
AU - Nicotera, Pierluigi
PY - 1993/12/1
Y1 - 1993/12/1
N2 - 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.
AB - 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.
KW - Ca channels
KW - Inositol polyphosphates
KW - Signal transduclion
UR - http://www.scopus.com/inward/record.url?scp=0027333581&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027333581&partnerID=8YFLogxK
M3 - Article
C2 - 8262335
AN - SCOPUS:0027333581
VL - 7
SP - 1507
EP - 1514
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 15
ER -