Characterization of calcium oscillations in normal and benzo[a]pyrene-treated clone 9 cells

Rola Barhoumi, Youssef Mouneimne, Igbal Awooda, Stephen H. Safe, Kirby C. Donnelly, Robert C. Burghardt

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Intracellular Ca2+ oscillations induced by oxytocin and vasopressin were analyzed in a rat liver cell line (Clone 9) in order to identify mechanisms by which benzo[α]pyrene (BaP) alters Ca2+ signaling patterns in these cells. Clone 9 cells exhibit an initial Ca2+ spike, followed by Ca2+ oscillations upon oxytocin or vasopressin treatment. The range of frequencies (maximum 110 mHz) was dependent on agonist concentration with a constant amplitude less than or equal to the amount of Ca2+ generated from the inositol trisphosphate (InsP3)-sensitive pool. This study examined contributions of extracellular and intracellular pools to the frequency of Ca2+ oscillations and the role of membrane channels, second messengers, and different pharmacological reagents on the regulation of oscillation frequency in both control and BaP-treated cells. Results indicated that the Ca2+ oscillations are mainly due to inositol 1,4,5-triphosphate (InsP3)-sensitive stores and that extra-cellular Ca2+ contributes to refilling of this intracellular Ca2+ pool. The frequency of Ca2+ oscillations is also sharply affected by protein kinase C activated by phospholipase C. In BaP-treated Clone 9 cells, basal Ca2+ levels were elevated and the frequency of Ca2+ oscillations was suppressed in a dose-dependent fashion. Suppression of Ca2+ oscillations is due, at least in part, to an effect of BaP on enhanced opening of K+ channels. This was confirmed by showing that inhibition of the K+ channel opening by tetraethylammonium chloride can reverse the effect of BaP on oxytocin-induced Ca2+ oscillations, and potentially decrease the toxicity of BaP.

Original languageEnglish (US)
Pages (from-to)444-450
Number of pages7
JournalToxicological Sciences
Volume68
Issue number2
DOIs
StatePublished - Aug 2002
Externally publishedYes

Keywords

  • BaP
  • Ca oscillations
  • Fluorescence microscopy
  • Laser cytometry
  • Oxytocin
  • Vasopressin

ASJC Scopus subject areas

  • Toxicology

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